|
1
|
Melo RCN, Rothenberg ME. Imaging eosinophil secretory granules: From storage containers to active, immune responder organelles. J Allergy Clin Immunol 2025; 155:414-417. [PMID: 39709031 DOI: 10.1016/j.jaci.2024.12.1069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 11/22/2024] [Accepted: 12/16/2024] [Indexed: 12/23/2024]
Affiliation(s)
- Rossana C N Melo
- Laboratory of Cellular Biology, Department of Biology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil.
| | - Marc E Rothenberg
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| |
Collapse
|
|
2
|
Danielson DT, Aguilera NS, Auerbach A. Head and Neck Classic Hodgkin, T and NK Lymphomas with Eosinophilia. Head Neck Pathol 2025; 19:10. [PMID: 39873807 PMCID: PMC11775375 DOI: 10.1007/s12105-025-01751-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Accepted: 01/11/2025] [Indexed: 01/30/2025]
Abstract
Eosinophilia is a notable feature in various hematological malignancies, including specific types of leukemias and lymphomas that may occur in the head and neck. In hematologic malignancies, eosinophilia can be primary, driven by genetic abnormalities, or secondary, resulting from cytokine and chemokine production by the neoplastic cells or the tumor microenvironment. This review examines the association between eosinophilia and head and neck hematolymphoid malignancies including Classic Hodgkin lymphoma, T-cell lymphoblastic leukemia, mature T and NK-cell lymphomas, and Langerhans cell histiocytosis. It explores the underlying mechanisms of eosinophilia in these malignancies, highlighting the role of chemokines and cytokines such as IL-5, TARC, and eotaxin. Recognition of eosinophilia may aid in the diagnosis of these conditions and understanding the mechanisms of eosinophilia may provide insights into potential prognostic implications and treatment strategies.
Collapse
Affiliation(s)
- David T Danielson
- Department of Pathology, Walter Reed National Military Medical Center, Bethesda, MD, USA.
| | | | | |
Collapse
|
|
3
|
Luo Y, Li Q, Liao Z, Luo Z. Unusual case of retroperitoneal hematoma and duodenal ulcerative bleeding after nephrectomy: Case report. Medicine (Baltimore) 2024; 103:e33765. [PMID: 38306569 PMCID: PMC10843467 DOI: 10.1097/md.0000000000033765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 04/24/2023] [Indexed: 02/04/2024] Open
Abstract
RATIONALE Retroperitoneal hematomas are relatively common in patients undergoing nephrectomy. Herein, we report an unusual case involving a giant retroperitoneal hematoma and subsequent duodenal ulcerative bleeding following a radical nephrectomy. PATIENT CONCERNS A 77-year-old woman was admitted to our hospital for lower back pain, and she had severe right hydronephrosis and a urinary tract infection. DIAGNOSES The patient was diagnosed and confirmed as high-grade urothelial carcinoma. INTERVENTIONS After ineffective conservative treatments, a right radical nephrectomy and ureteral stump resection were performed. The patient received proton pump inhibitors to prevent stress ulcer formation and bleeding. On the first day post-surgery, she had normal gastrointestinal (GI) endoscopy findings. On the second day post-surgery, abdominal computed tomography revealed a retroperitoneal hematoma. Notably, 14 days post-surgery, massive GI bleeding occurred, and GI endoscopy identified an almost perforated ulcer in the bulbar and descending duodenum. OUTCOMES The patient died on day 15 after surgery. LESSONS Duodenal ulceration and bleeding might occur following a retroperitoneal hematoma in patients treated with nephrectomy. Timely intervention may prevent duodenal ulcers and complications, and thus could be a promising life-saving intercession.
Collapse
Affiliation(s)
- Yong Luo
- Hengyang Medical School, University of South China; Trauma Centre & Emergency Department, The Second Affiliated Hospital of the University of South China, Hengyang, P.R. China
| | - Qing Li
- Hengyang Medical School, University of South China; Trauma Centre & Emergency Department, The Second Affiliated Hospital of the University of South China, Hengyang, P.R. China
| | - Zhanchen Liao
- Trauma Centre & Emergency Department, and Institute of Urology and Organ Transplantation, The Second Affiliated Hospital of the University of South China, Hengyang, P.R. China
| | - Zhigang Luo
- Trauma Centre & Emergency Department, and Institute of Urology and Organ Transplantation, The Second Affiliated Hospital of the University of South China, Hengyang, P.R. China
| |
Collapse
|
|
4
|
Elbahoty M, Elnaggar S, Soror N, Elkeraie A, Youssef A. Co-occurrence of Idiopathic Hypereosinophilic Syndrome in End-Stage Renal Disease Patients Undergoing Maintenance Hemodialysis. Cureus 2024; 16:e53758. [PMID: 38465088 PMCID: PMC10921820 DOI: 10.7759/cureus.53758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2024] [Indexed: 03/12/2024] Open
Abstract
Hypereosinophilic syndrome (HES) is defined as the presence of (1) peripheral blood eosinophilia >1.5 x 109/L for at least one month, (2) evidence of eosinophil-mediated organ damage and/or dysfunction, and (3) exclusion of other potential causes of eosinophilia. In hemodialysis patients, HES has been associated with manifestations because of low blood pressure or gastrointestinal symptoms that result in dialysis intolerance. Very few cases of HES co-occurrence in dialysis patients have been reported in the literature, and their clinical characteristics are not fully understood. Here, we report two end-stage renal disease patients diagnosed with idiopathic HES while undergoing maintenance hemodialysis. The first patient presented with unexplained persistent pruritus and intradialytic hypotension, which started 10 minutes after the dialysis session initiation. Hematologic studies revealed hypereosinophilia which remarkably improved on steroid therapy. The second patient was accidentally discovered with asymptomatic persistent hypereosinophilia. His blood counts improved initially on interferon treatment before achieving full remission on steroid therapy. Neither of the two patients reported any history of allergy or atopic manifestations. Our case report sheds light on the possible occurrence of HES in hemodialysis patients which may be confused with other dialysis-related complications. Although steroids remain the mainstay of treatment, the optimal dose and duration of treatment remain unknown.
Collapse
Affiliation(s)
- Mohamed Elbahoty
- Department of Pathology, University of Alabama at Birmingham, Birmingham, USA
- Department of Internal Medicine, Hematology Unit, Faculty of Medicine, Alexandria University, Alexandria, EGY
| | - Sherine Elnaggar
- Nephrology and Hemodialysis Unit, Alexandria University Hospitals, Alexandria, EGY
| | - Nooran Soror
- Department of Internal Medicine, Hematology Unit, Faculty of Medicine, Alexandria University, Alexandria, EGY
| | - Ahmed Elkeraie
- Department of Internal Medicine, Nephrology and Hemodialysis Unit, Faculty of Medicine, Alexandria University, Alexandria, EGY
| | - Ayman Youssef
- Anesthesiology and Critical Care, Duke University Medical Center, Durham, USA
- Department of Internal Medicine, Hematology Unit, Faculty of Medicine, Alexandria University, Alexandria, EGY
| |
Collapse
|
|
5
|
Vieira BM, de São José VS, Niemeyer Filho PS, Moura-Neto V. Eosinophils induces glioblastoma cell suppression and apoptosis - Roles of GM-CSF and cysteinyl-leukotrienes. Int Immunopharmacol 2023; 123:110729. [PMID: 37536182 DOI: 10.1016/j.intimp.2023.110729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 07/10/2023] [Accepted: 07/27/2023] [Indexed: 08/05/2023]
Abstract
BACKGROUND Glioblastoma is the most common and lethal primary brain tumor in adults. Despite the available cancer treatments, the recurrence of the tumor is high, and the survival rate is low. New approaches to antitumor therapies are needed. Eosinophils are prominent in allergic diseases and accumulate in several human brain tumors. Recently, the antitumor role of eosinophils has been targeted as eosinophils release several cytotoxic factors that induce cell impairment and death. OBJECTIVE Here we aim to evaluate the interaction of the eosinophil and glioblastoma cells, the mechanism involved in the potential killing of the glioblastoma cells by the eosinophils, and how allergy/asthma could confer a better glioblastoma prognosis. METHODS Eosinophils and serum from asthmatic and non-asthmatic donors were cultivated with different glioblastoma cell lines. RESULTS Glioblastoma cells recruit eosinophils via GM-CSF signaling, activating and increasing eosinophil survivability and function on a GM-CSF-dependent manner. Eosinophils reduce glioblastoma cells metabolism, proliferation, and migration, via Fas/FasL. Cysteinyl-leukotrienes are accounted for the asthmatic serum enhancement of the glioblastoma cell migration and proliferation. Cysteinyl-leukotrienes enhance glioblastoma cell proliferation and migration, albeit activate eosinophils that suppress glioblastoma cells. CONCLUSION Eosinophils have the potential to be key cells on glioblastoma therapeutics, as allergy and eosinophilia are correlated with a better glioblastoma prognosis. Eosinophils are elicited and attach to glioblastoma cells, where, by its cytotoxic function, via Fas/FasL, hind glioblastoma cell metabolism, proliferation, migration, and induce cell death.
Collapse
Affiliation(s)
- Bruno Marques Vieira
- Laboratório de Biomedicina do Cérebro, Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro, Brazil.
| | - Vitória Santório de São José
- Laboratório de Biomedicina do Cérebro, Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro, Brazil; Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio®), Instituto Nacional de Ciência e Tecnologia de Fármacos e Medicamentos (INCT-INOFAR), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Paulo Soares Niemeyer Filho
- Laboratório de Biomedicina do Cérebro, Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro, Brazil
| | - Vivaldo Moura-Neto
- Laboratório de Biomedicina do Cérebro, Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro, Brazil
| |
Collapse
|
|
6
|
Valent P, Klion AD, Roufosse F, Simon D, Metzgeroth G, Leiferman KM, Schwaab J, Butterfield JH, Sperr WR, Sotlar K, Vandenberghe P, Hoermann G, Haferlach T, Moriggl R, George TI, Akin C, Bochner BS, Gotlib J, Reiter A, Horny HP, Arock M, Simon HU, Gleich GJ. Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy 2023; 78:47-59. [PMID: 36207764 PMCID: PMC9797433 DOI: 10.1111/all.15544] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 09/20/2022] [Accepted: 10/01/2022] [Indexed: 12/31/2022]
Abstract
Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE), HE-induced organ damage is often encountered and may lead to the diagnosis of a hypereosinophilic syndrome (HES). A number of known mechanisms and etiologies contribute to the development of HE and HES. Based on these etiologies and the origin of eosinophils, HE and HES are divided into primary forms where eosinophils are clonal cells, reactive forms where an underlying reactive or neoplastic condition is detected and eosinophils are considered to be "non-clonal" cells, and idiopathic HE and HES in which neither a clonal nor a reactive underlying pathology is detected. Since 2012, this classification and the related criteria have been widely accepted and regarded as standard. However, during the past few years, new developments in the field and an increasing number of markers and targets have created a need to update these criteria and the classification of HE and HES. To address this challenge, a Working Conference on eosinophil disorders was organized in 2021. In this conference, a panel of experts representing the relevant fields, including allergy, dermatology, hematology, immunology, laboratory medicine, and pathology, met and discussed new markers and concepts as well as refinements in definitions, criteria and classifications of HE and HES. The outcomes of this conference are presented in this article and should assist in the diagnosis and management of patients with HE and HES in daily practice and in the preparation and conduct of clinical trials.
Collapse
Affiliation(s)
- Peter Valent
- Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria,Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Austria,Correspondence: Peter Valent, M.D. Department of Medicine I, Division of Hematology & Hemostaseology and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria, Phone: 43 1 40400 4415; Fax: 43 1 40040 4030,
| | - Amy D. Klion
- Human Eosinophil Section, Laboratory of Parasitic Diseases, NIH/NIAID, Bethesda, MD, USA
| | - Florence Roufosse
- Department of Internal Medicine, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Dagmar Simon
- Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Georgia Metzgeroth
- Department of Hematology and Oncology, University Hospital Mannheim - Heidelberg University, Germany
| | | | - Juliana Schwaab
- Department of Hematology and Oncology, University Hospital Mannheim - Heidelberg University, Germany
| | | | - Wolfgang R. Sperr
- Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria,Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Austria
| | - Karl Sotlar
- Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
| | - Peter Vandenberghe
- Division of Hematology, University Hospital Leuven and Department of Human Genetics, KU Leuven, Belgium
| | | | | | - Richard Moriggl
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, Austria
| | - Tracy I. George
- Department of Pathology, University of Utah, Salt Lake City, UT, USA
| | - Cem Akin
- Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, MI, USA
| | - Bruce S. Bochner
- Northwestern University Feinberg School of Medicine, Division of Allergy and Immunology, Chicago, IL, USA
| | - Jason Gotlib
- Stanford Cancer Institute/Stanford University School of Medicine, Stanford, CA, USA
| | - Andreas Reiter
- Department of Hematology and Oncology, University Hospital Mannheim - Heidelberg University, Germany
| | - Hans-Peter Horny
- Institute of Pathology, Ludwig Maximilian University Munich (LMU), Munich, Germany
| | - Michel Arock
- Department of Hematological Biology, Pitié-Salpêtrière Hospital, Pierre et Marie Curie University (UPMC), Paris, France
| | - Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, Bern, Switzerland,Institute of Biochemistry, Brandenburg Medical School, Neuruppin, Germany
| | - Gerald J. Gleich
- Departments of Dermatology and Medicine, University of Utah Health, Salt Lake City, UT, USA
| |
Collapse
|
|
7
|
Ahirwar LK, Sharma S. Elevated levels of interleukins, leukocyte protein and cathelicidin antimicrobial peptide are strongly associated with early to mid-stage of Pythium insidiosum infection in rabbit corneas. Curr Eye Res 2022; 47:677-687. [PMID: 35179411 DOI: 10.1080/02713683.2021.2023192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
PURPOSE Corneal infection in humans caused by Pythium insidiosum can lead to blindness and the host ocular immune response to it is less studied. Herein, we investigate the expression of mediators of innate and adaptive immune responses in a rabbit model. METHODS P. insidiosum zoospores were injected intracorneally in right eye of the nine New Zealand White rabbits while left eye was injected with 1XPBS. RT-qPCR and multiplex ELISA (mELISA) were used to study the expression of antimicrobial peptides (AMPs) and immune mediators in infected cornea on 3rd, 7th and 9th day of post-infection(PI). STRING-11.0 analysis was used to predict the interactions of immune mediators. mRNA expressions of pathogen recognition receptors (PRRs) were determined in human corneal epithelial cells (HCECs) stimulated with P. insidiosum zoospores. Data was analyzed using one-way ANOVA with Post-Hoc Tukey HSD test and p-value <0.05 was considered significant. RESULTS mRNA expression assay for IL-1β, IL-6, IL-8 and Cathelicidin antimicrobial peptide (CAP)-18 showed significant upregulation (p-value <0.05) on 7thday post-infection (PI) compared to 3rd and 9thday while Leukocyte protein (LeukoP) was elevated significantly on 3rd day followed by 7th and 9th day PI . Only IL-17A among other adaptive immune cytokines showed significant upregulation on 7thday compared to 9thday PI. Expressed in pg/mL, mELISA showed significant higher levels (p-value <0.05) of IL-1β, IL-8 in infected tissue in each of the time points compared to control. STRING analysis revealed co-expression of IL-1β, IL-8 and IL-6. Among PRRs, Dectin 1 and TLR4 showed significant upregulation in HCECs at 12hrs compared to 6hrs. CONCLUSION In the rabbit P. insidiosum keratitis model, innate immune mediators: IL-1β, IL-8, IL-6, AMPs: LeukoP and CAP-18 are strongly associated in early to mid-stage of corneal infection. Dectin 1 and TLR4 were observed to be associated with recognition of P. insidiosum.
Collapse
Affiliation(s)
- Lalit Kishore Ahirwar
- Jhaveri Microbiology Centre, Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Kallam Anji Reddy Campus, L. V. Prasad Marg, Banjara Hills, Hyderabad-500034, India
| | - Savitri Sharma
- Jhaveri Microbiology Centre, Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Kallam Anji Reddy Campus, L. V. Prasad Marg, Banjara Hills, Hyderabad-500034, India
| |
Collapse
|
|
8
|
Arifa RDN, Brito CB, de Paula TP, Lima RL, Menezes‐Garcia Z, Cassini‐Vieira P, Vilas Boas FA, Queiroz‐Junior CM, da Silva JM, da Silva TA, Barcelos LS, Fagundes CT, Teixeira MM, Souza DG. Eosinophil plays a crucial role in intestinal mucositis induced by antineoplastic chemotherapy. Immunology 2021; 165:355-368. [DOI: 10.1111/imm.13442] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 12/01/2021] [Accepted: 12/15/2021] [Indexed: 12/01/2022] Open
Affiliation(s)
- Raquel D N Arifa
- Laboratory of Microorganism‐Host Interaction Department of Microbiology
| | - Camila B Brito
- Laboratory of Microorganism‐Host Interaction Department of Microbiology
| | - Talles P de Paula
- Laboratory of Microorganism‐Host Interaction Department of Microbiology
| | - Renata L Lima
- Laboratory of Microorganism‐Host Interaction Department of Microbiology
| | | | | | | | - Celso M Queiroz‐Junior
- Department of Oral Pathology and Surgery Faculty of Dentistry Universidade Federal de Minas Gerais Belo Horizonte, Minas Gerais Brazil
| | - Janine M da Silva
- Department of Oral Pathology and Surgery Faculty of Dentistry Universidade Federal de Minas Gerais Belo Horizonte, Minas Gerais Brazil
| | - Tarcília A da Silva
- Department of Oral Pathology and Surgery Faculty of Dentistry Universidade Federal de Minas Gerais Belo Horizonte, Minas Gerais Brazil
| | | | - Caio T. Fagundes
- Laboratory of Microorganism‐Host Interaction Department of Microbiology
- Center for Drug Research and Development of Pharmaceuticals
| | - Mauro M Teixeira
- Center for Drug Research and Development of Pharmaceuticals
- Department of Biochemistry and Immunology Institute of Biological Sciences
| | - Daniele G. Souza
- Laboratory of Microorganism‐Host Interaction Department of Microbiology
| |
Collapse
|
|
9
|
Komlósi ZI, van de Veen W, Kovács N, Szűcs G, Sokolowska M, O'Mahony L, Akdis M, Akdis CA. Cellular and molecular mechanisms of allergic asthma. Mol Aspects Med 2021; 85:100995. [PMID: 34364680 DOI: 10.1016/j.mam.2021.100995] [Citation(s) in RCA: 107] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/13/2021] [Accepted: 07/15/2021] [Indexed: 12/21/2022]
Abstract
Asthma is a chronic disease of the airways, which affects more than 350 million people worldwide. It is the most common chronic disease in children, affecting at least 30 million children and young adults in Europe. Asthma is a complex, partially heritable disease with a marked heterogeneity. Its development is influenced both by genetic and environmental factors. The most common, as well as the most well characterized subtype of asthma is allergic eosinophilic asthma, which is characterized by a type 2 airway inflammation. The prevalence of asthma has substantially increased in industrialized countries during the last 60 years. The mechanisms underpinning this phenomenon are incompletely understood, however increased exposure to various environmental pollutants probably plays a role. Disease inception is thought to be enabled by a disadvantageous shift in the balance between protective and harmful lifestyle and environmental factors, including exposure to protective commensal microbes versus infection with pathogens, collectively leading to airway epithelial cell damage and disrupted barrier integrity. Epithelial cell-derived cytokines are one of the main drivers of the type 2 immune response against innocuous allergens, ultimately leading to infiltration of lung tissue with type 2 T helper (TH2) cells, type 2 innate lymphoid cells (ILC2s), M2 macrophages and eosinophils. This review outlines the mechanisms responsible for the orchestration of type 2 inflammation and summarizes the novel findings, including but not limited to dysregulated epithelial barrier integrity, alarmin release and innate lymphoid cell stimulation.
Collapse
Affiliation(s)
- Zsolt I Komlósi
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad Sqr. 4, 1089, Budapest, Hungary.
| | - Willem van de Veen
- Swiss Institute of Allergy and Asthma Research (SIAF), Hermann-Burchard Strasse 9, CH7265, Davos Wolfgand, Switzerland; Christine Kühne - Center for Allergy Research and Education, Davos, Switzerland
| | - Nóra Kovács
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad Sqr. 4, 1089, Budapest, Hungary; Lung Health Hospital, Munkácsy Mihály Str. 70, 2045, Törökbálint, Hungary
| | - Gergő Szűcs
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad Sqr. 4, 1089, Budapest, Hungary; Department of Pulmonology, Semmelweis University, Tömő Str. 25-29, 1083, Budapest, Hungary
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF), Hermann-Burchard Strasse 9, CH7265, Davos Wolfgand, Switzerland; Christine Kühne - Center for Allergy Research and Education, Davos, Switzerland
| | - Liam O'Mahony
- Department of Medicine and School of Microbiology, APC Microbiome Ireland, University College Cork, Ireland
| | - Mübeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), Hermann-Burchard Strasse 9, CH7265, Davos Wolfgand, Switzerland; Christine Kühne - Center for Allergy Research and Education, Davos, Switzerland
| | - Cezmi A Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), Hermann-Burchard Strasse 9, CH7265, Davos Wolfgand, Switzerland; Christine Kühne - Center for Allergy Research and Education, Davos, Switzerland
| |
Collapse
|
|
10
|
Valent P, Degenfeld-Schonburg L, Sadovnik I, Horny HP, Arock M, Simon HU, Reiter A, Bochner BS. Eosinophils and eosinophil-associated disorders: immunological, clinical, and molecular complexity. Semin Immunopathol 2021; 43:423-438. [PMID: 34052871 PMCID: PMC8164832 DOI: 10.1007/s00281-021-00863-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 04/29/2021] [Indexed: 12/15/2022]
Abstract
Eosinophils and their mediators play a crucial role in various reactive states such as bacterial and viral infections, chronic inflammatory disorders, and certain hematologic malignancies. Depending on the underlying pathology, molecular defect(s), and the cytokine- and mediator-cascades involved, peripheral blood and tissue hypereosinophilia (HE) may develop and may lead to organ dysfunction or even organ damage which usually leads to the diagnosis of a HE syndrome (HES). In some of these patients, the etiology and impact of HE remain unclear. These patients are diagnosed with idiopathic HE. In other patients, HES is diagnosed but the etiology remains unknown — these patients are classified as idiopathic HES. For patients with HES, early therapeutic application of agents reducing eosinophil counts is usually effective in avoiding irreversible organ damage. Therefore, it is important to systematically explore various diagnostic markers and to correctly identify the disease elicitors and etiology. Depending on the presence and type of underlying disease, HES are classified into primary (clonal) HES, reactive HES, and idiopathic HES. In most of these patients, effective therapies can be administered. The current article provides an overview of the pathogenesis of eosinophil-associated disorders, with special emphasis on the molecular, immunological, and clinical complexity of HE and HES. In addition, diagnostic criteria and the classification of eosinophil disorders are reviewed in light of new developments in the field.
Collapse
Affiliation(s)
- Peter Valent
- Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, 18-20 1090, Vienna, Austria. .,Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
| | - Lina Degenfeld-Schonburg
- Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, 18-20 1090, Vienna, Austria
| | - Irina Sadovnik
- Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, 18-20 1090, Vienna, Austria.,Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria
| | - Hans-Peter Horny
- Institute of Pathology, Ludwig Maximilian University, Munich, Germany
| | - Michel Arock
- Laboratory of Hematology, Pitié-Salpêtrière Hospital, Paris, France
| | - Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, Bern, Switzerland.,Department of Clinical Immunology and Allergology, Sechenov University, Moscow, Russia.,Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
| | - Andreas Reiter
- Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany
| | - Bruce S Bochner
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| |
Collapse
|
|
11
|
Mutsuyoshi Y, Hirai K, Morino J, Kaneko S, Minato S, Yanai K, Ishii H, Matsuyama M, Kitano T, Aomatsu A, Miyazawa H, Ito K, Ueda Y, Ookawara S, Morishita Y. Idiopathic hypereosinophilic syndrome in hemodialysis patients: Case reports. Medicine (Baltimore) 2021; 100:e25164. [PMID: 33725918 PMCID: PMC7969317 DOI: 10.1097/md.0000000000025164] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 02/25/2021] [Indexed: 01/05/2023] Open
Abstract
RATIONALE Herein, we report 3 hemodialysis patients with idiopathic hypereosinophilic syndrome who were successfully treated using corticosteroid therapy. PATIENT CONCERNS Case 1 was a 63-year-old man who was undergoing hemodialysis because of bilateral nephrectomy and developed hypereosinophilia with digestive symptoms, myocardial injury, and intradialytic hypotension. Case 2 was an 83-year-old man who was undergoing hemodialysis because of nephrosclerosis and developed hypereosinophilia with pruritus, myocardial injury, and intradialytic hypotension. Case 3 was a 59-year-old man who was undergoing hemodialysis because of diabetic nephropathy and developed hypereosinophilia with pruritus, myocardial injury, and intradialytic hypotension. DIAGNOSES All 3 patients presented with hypereosinophilia (eosinophil count ≥1500 /μL for more than 1 month) and multiple-organ involvement (intradialytic hypotension, cardiac injury, digestive symptoms, and allergic dermatitis). A specific cause for the hypereosinophilia was not identified by systemic computed tomography, electrocardiography, echocardiography, bone marrow examination, or blood tests. Furthermore, Case 2 and 3 had not recently started taking any new drugs and drug-induced lymphocyte stimulation tests were negative in Case 1. Therefore, they were diagnosed with idiopathic hypereosinophilic syndrome. INTERVENTIONS All 3 patients received corticosteroid therapy with prednisolone at a dose of 40 mg/d, 30 mg/d, and 60 mg/d in Case 1, 2, and 3, respectively. OUTCOMES Their digestive symptoms, pruritus, intradialytic hypotension, and serum troponin I concentrations were immediately improved alongside reductions in their eosinophil counts. LESSONS There have been few case reports of idiopathic hypereosinophilic syndrome in patients undergoing hemodialysis. We believe that recording of the clinical findings and treatments of such patients is mandatory to establish the optimal management of idiopathic hypereosinophilic syndrome.
Collapse
|
|
12
|
David B, Bafadhel M, Koenderman L, De Soyza A. Eosinophilic inflammation in COPD: from an inflammatory marker to a treatable trait. Thorax 2021; 76:188-195. [PMID: 33122447 PMCID: PMC7815887 DOI: 10.1136/thoraxjnl-2020-215167] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 07/28/2020] [Accepted: 10/01/2020] [Indexed: 12/20/2022]
Abstract
The heterogeneity of chronic obstructive pulmonary disease (COPD) creates many diagnostic, prognostic, treatment and management challenges, as the pathogenesis of COPD is highly complex and the underlying cellular and molecular mechanisms remain poorly understood. A reliable, easy-to-measure, clinically relevant biomarker would be invaluable for improving outcomes for patients. International and national guidance for COPD suggests using blood eosinophil counts as a biomarker to help estimate likely responsiveness to inhaled corticosteroids (ICS) and, potentially, to aid effective management strategies. However, with the mechanism underlying the association between higher eosinophil levels and ICS effect unknown, use of the blood eosinophil count in COPD continues to be widely debated by the respiratory community.Two international meetings involving respiratory medicine specialists, immunologists and primary and secondary care clinicians were held in November 2018 and March 2019, facilitated and funded by GlaxoSmithKline plc. The aims of these meetings were to explore the role of eosinophils in the disease processes of COPD and as prognostic and diagnostic markers, and to identify areas of deficient knowledge that warrant further research. The consensus views of the attendees on key topics, contextualised with current literature, are summarised in this review article, with the aim of aiding ongoing research into the disease processes of COPD and the development of biomarkers to aid clinical management.Under certain conditions, eosinophils can be recruited to the lung, and increasing evidence supports a role for eosinophilic inflammation in some patients with COPD. Infiltration of eosinophils across the bronchial vascular epithelium into the airways is promoted by the actions of immunoregulatory cells, cytokines and chemokines, where eosinophil-mediated inflammation is driven by the release of proinflammatory mediators.Multiple studies and two meta-analyses suggest peripheral blood eosinophils may correlate positively with an increased likelihood of exacerbation reduction benefits of ICS in COPD. The studies, however, vary in design and duration and by which eosinophil levels are viewed as predictive of an ICS response. Generally, the response was seen when eosinophil levels were 100-300 cells/µL (or higher), levels which are traditionally viewed within the normal range. Some success with interleukin-5-targeted therapy suggests that the eosinophilic phenotype may be a treatable trait.The use of biomarkers could help to stratify treatment for COPD-the goal of which is to improve patient outcomes. Some evidence supports eosinophils as a potential biomarker of a treatable trait in COPD, though it is still lacking and research is ongoing. A unified consensus and a practical, accessible and affordable method of utilising any biomarker for COPD was thought to be of most importance. Challenges around its utilisation may include presenting a clear and pragmatic rationale for biomarker-driven therapy, guidance on ICS withdrawal between primary and secondary care and a lack of financial incentives supporting broad application in clinical practice. Future treatments should, perhaps, be more targeted rather than assuming the primary disease label (COPD or asthma) will define treatment response.
Collapse
Affiliation(s)
- Benjamin David
- Research & Development, GlaxoSmithKline plc, Middlesex, UK
| | - Mona Bafadhel
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Leo Koenderman
- Department of Respiratory Medicine and Center for Translational Immunology (CTI), University Medical Center Utrecht, Utrecht, The Netherlands
| | - Antony De Soyza
- Institute of Cellular Medicine, NIHR Biomedical Research Centre for Aging and Department of Respiratory Medicine, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK
| |
Collapse
|
|
13
|
Choi BS. Is determining nasal eosinophil count and nasal eosinophil peroxidase concentration clinically useful in children with rhinits? KOREAN JOURNAL OF PEDIATRICS 2019; 62:342-343. [PMID: 31319644 PMCID: PMC6753316 DOI: 10.3345/kjp.2019.00556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 07/05/2019] [Indexed: 11/27/2022]
Affiliation(s)
- Bong Seok Choi
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea
| |
Collapse
|
|
14
|
Vieira BM, de Souza dos Santos MC, Masid-de-Brito D, Queto T, Alves TM, Zani CL, Gaspar-Elsas MIC, Xavier-Elsas P. Potent stimulation of eosinopoiesis in murine bone-marrow by myriadenolide is mediated by cysteinyl-leukotriene signaling. Int Immunopharmacol 2019; 72:82-91. [DOI: 10.1016/j.intimp.2019.04.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 03/29/2019] [Accepted: 04/01/2019] [Indexed: 12/22/2022]
|
|
15
|
Tashkin DP, Wechsler ME. Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2018; 13:335-349. [PMID: 29403271 PMCID: PMC5777380 DOI: 10.2147/copd.s152291] [Citation(s) in RCA: 106] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD.
Collapse
Affiliation(s)
- Donald P Tashkin
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | | |
Collapse
|
|
16
|
Chen B, Yang Z, Lu H, Wei C, Wang F, Liu C. Eosinophilic gastroenteritis presenting as upper gastrointestinal hematoma and ulcers after endoscopic biopsy: A case report and literature review. Medicine (Baltimore) 2017; 96:e8075. [PMID: 28906408 PMCID: PMC5604677 DOI: 10.1097/md.0000000000008075] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2017] [Revised: 08/19/2017] [Accepted: 08/23/2017] [Indexed: 12/11/2022] Open
Abstract
RATIONALE Eosinphilic gastroenteritis (EG) is a gastrointestinal disorder characterized by eosinophilic infiltration with various manifestations. The diagnosis is usually confirmed by an endoscopic biopsy, which is considered a safe and routine procedure for the majority. PATIENT CONCERNS We report a 54-year-old male who was presented with intermittent periumbilical pain and melena, and only revealed verrucous gastritis by endoscopy. DIAGNOSES The patient's condition worsened two days after the endoscopic biopsy, and another endoscopy found hematoma and ulcers in upper gastrointestinal tract. He was diagnosed with EG by the pathological analysis of biopsy specimen. INTERVENTIONS Oral methylprednisolone and Montelukast were prescribed. OUTCOMES The patient got remission after initiation of the treatment. LESSONS This case highlights an extremely rare but potentially severe complication of endoscopic biopsies in patients with EG. Physicians should be cautious with hematoma or ulceration, and consider it in such patients who undergo this procedure.
Collapse
Affiliation(s)
- Biqin Chen
- Department of Gastroenterology and Hepatology, Jinling Hospital, School of Medicine, Southern Medical University
| | - Zhao Yang
- Department of Gastroenterology and Hepatology, Jinling Hospital, School of Medicine, Southern Medical University
| | - Heng Lu
- Department of Gastroenterology and Hepatology, Jinling Hospital
| | - Cheng Wei
- Department of Gastroenterology and Hepatology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China
| | - Fangyu Wang
- Department of Gastroenterology and Hepatology, Jinling Hospital, School of Medicine, Southern Medical University
| | - Chang Liu
- Department of Gastroenterology and Hepatology, Jinling Hospital
| |
Collapse
|
|
17
|
Tsang MSM, Jiao D, Chan BCL, Hon KL, Leung PC, Lau CBS, Wong ECW, Cheng L, Chan CKM, Lam CWK, Wong CK. Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation. Molecules 2016; 21:519. [PMID: 27104513 PMCID: PMC6274171 DOI: 10.3390/molecules21040519] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 04/14/2016] [Accepted: 04/15/2016] [Indexed: 12/22/2022] Open
Abstract
Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p < 0.05). Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils.
Collapse
Affiliation(s)
- Miranda S M Tsang
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
| | - Delong Jiao
- Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.
| | - Ben C L Chan
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
| | - Kam-Lun Hon
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
| | - Ping C Leung
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
| | - Clara B S Lau
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
- Li Dak Sum Yip Yio Chin R & D Centre for Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
| | - Eric C W Wong
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
| | - Ling Cheng
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
| | - Carmen K M Chan
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
| | - Christopher W K Lam
- State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.
| | - Chun K Wong
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China.
- Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.
- Li Dak Sum Yip Yio Chin R & D Centre for Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
| |
Collapse
|
|
18
|
George L, Brightling CE. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease. Ther Adv Chronic Dis 2016; 7:34-51. [PMID: 26770668 DOI: 10.1177/2040622315609251] [Citation(s) in RCA: 225] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10-40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments.
Collapse
Affiliation(s)
- Leena George
- Institute for Lung Health, NIHR Respiratory Biomedical Research Unit, Department of Infection, Immunity and Inflammation, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Christopher E Brightling
- Institute for Lung Health, Clinical Science Wing, University Hospital of Leicester, Leicester LE3 9QP, UK
| |
Collapse
|
|
19
|
Valent P, Klion AD, Rosenwasser LJ, Arock M, Bochner BS, Butterfield JH, Gotlib J, Haferlach T, Hellmann A, Horny HP, Leiferman KM, Metzgeroth G, Matsumoto K, Reiter A, Roufosse F, Rothenberg ME, Simon HU, Sotlar K, Vandenberghe P, Weller PF, Gleich GJ. ICON: Eosinophil Disorders. World Allergy Organ J 2013; 5:174-81. [PMID: 23282419 PMCID: PMC3651188 DOI: 10.1097/wox.0b013e31827f4192] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Peter Valent
- 1Department of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria 2Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, NIH/NIAID, Bethesda, MD 3Children's Mercy Hospital, Kansas City, MO 4LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, Cachan, France 5Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 6Division of Allergic Diseases, Mayo Clinic, Rochester, MN 7Division of Hematology, Stanford Cancer Center, Stanford, CA 8MLL Münchner Leukämielabor, Munich, Germany 9Department of Hematology, Medical University School of Gdansk, Gdańsk, Poland 10Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany 11Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, UT 12III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany 13Department of Allergy and Immunology, National Research Institute for Children's Health and Development, Tokyo, Japan 14Department of Internal Medicine, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium 15Division of Allergy and Immunology, Cincinnati Children's Hospital, Medical Center, Cincinnati, OH 16Institute of Pharmacology, University of Bern, Bern, Switzerland 17Center for Human Genetics, University Hospitals Leuven and Katholieke Universiteit Leuven, Leuven, Belgium 18Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 19Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, UT
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
20
|
Lee JJ, Jacobsen EA, Ochkur SI, McGarry MP, Condjella RM, Doyle AD, Luo H, Zellner KR, Protheroe CA, Willetts L, Lesuer WE, Colbert DC, Helmers RA, Lacy P, Moqbel R, Lee NA. Human versus mouse eosinophils: "that which we call an eosinophil, by any other name would stain as red". J Allergy Clin Immunol 2012; 130:572-84. [PMID: 22935586 DOI: 10.1016/j.jaci.2012.07.025] [Citation(s) in RCA: 156] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2012] [Revised: 07/25/2012] [Accepted: 07/25/2012] [Indexed: 12/20/2022]
Abstract
The respective life histories of human subjects and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiologic pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils, their effector functions, or both. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide experimental details comparing and contrasting eosinophils and eosinophil effector functions in human subjects versus mice. In particular, our review will provide a summation and an easy-to-use reference guide to important studies demonstrating that although differences exist, more often than not, their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function but instead species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients.
Collapse
Affiliation(s)
- James J Lee
- Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
21
|
Valent P, Gleich GJ, Reiter A, Roufosse F, Weller PF, Hellmann A, Metzgeroth G, Leiferman KM, Arock M, Sotlar K, Butterfield JH, Cerny-Reiterer S, Mayerhofer M, Vandenberghe P, Haferlach T, Bochner BS, Gotlib J, Horny HP, Simon HU, Klion AD. Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field. Expert Rev Hematol 2012; 5:157-76. [PMID: 22475285 DOI: 10.1586/ehm.11.81] [Citation(s) in RCA: 117] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Eosinophils and their products play an essential role in the pathogenesis of various reactive and neoplastic disorders. Depending on the underlying disease, molecular defect and involved cytokines, hypereosinophilia may develop and may lead to organ damage. In other patients, persistent eosinophilia is accompanied by typical clinical findings, but the causative role and impact of eosinophilia remain uncertain. For patients with eosinophil-mediated organ pathology, early therapeutic intervention with agents reducing eosinophil counts can be effective in limiting or preventing irreversible organ damage. Therefore, it is important to approach eosinophil disorders and related syndromes early by using established criteria, to perform all appropriate staging investigations, and to search for molecular targets of therapy. In this article, we review current concepts in the pathogenesis and evolution of eosinophilia and eosinophil-related organ damage in neoplastic and non-neoplastic conditions. In addition, we discuss classifications of eosinophil disorders and related syndromes as well as diagnostic algorithms and standard treatment for various eosinophil-related disorders.
Collapse
Affiliation(s)
- Peter Valent
- Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
22
|
Traumatic ulcerative granuloma with stromal eosinophilia: a lesion with alarming histopathologic presentation and benign clinical course. Am J Dermatopathol 2011; 33:192-4. [PMID: 20966736 DOI: 10.1097/dad.0b013e3181e26db0] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a chronic, benign, self-limiting lesion of the oral mucosa. Clinically, the ulceration is characterized by the presence of indurated elevated borders and may resemble pyogenic granuloma or even squamous cell carcinoma of the mouth. Pathogenesis of the lesion is unclear. Although it had been suggested that TUGSE may represent a CD30+ lymphoproliferative disorder, this theory is currently not supported by evidence. We are presenting a classic example of TUGSE, its clinical course, differential diagnosis, and treatment.
Collapse
|
|
23
|
Kim M, Chung J, Lee C, Jung J, Kwon Y, Lee K. A peptide binding to dimerized translationally controlled tumor protein modulates allergic reactions. J Mol Med (Berl) 2011; 89:603-10. [PMID: 21384150 DOI: 10.1007/s00109-011-0740-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2010] [Revised: 01/30/2011] [Accepted: 02/10/2011] [Indexed: 11/28/2022]
Abstract
Translationally controlled tumor protein (TCTP) is believed to be involved in a variety of inflammatory processes: secretion of histamine and cytokines such as IL-4, IL-8, IL-13, and granulocyte/macrophage colony-stimulating factor; chemoattraction for eosinophils; augmentation of B cell proliferation; and immunoglobulin production, thereby potentially regulating allergic phenomena. In a previous study, we showed that the cytokine-releasing activity of extracellular TCTP is generated only when TCTP dimerizes via the intermolecular disulfide bond of NH(2)-terminal truncated TCTP implying that the dimerized TCTP (dTCTP) promotes the inflammatory phenomena. Modulation of dTCTP, thus, may offer a strategy for the treatment of chronic allergic diseases. In this study, we searched for dTCTP-binding peptides (dTBPs) by screening a phage-displayed 7-mer peptide library. We identified one peptide in the library, designated as dTBP2, which showed higher affinity to dTCTP than to full-length, monomeric TCTP. dTBP2 inhibited the induction of IL-8 by dTCTP from BEAS-2B cells. dTBP2 also reduced symptom score and eosinophil infiltration in a mouse rhinitis model. This study suggests that the dTBP2 binding to dTCTP modulates the release of inflammatory mediators of dTCTP. This result may provide a rational strategy for the treatment of allergic diseases.
Collapse
Affiliation(s)
- Miyoung Kim
- College of Pharmacy, Center for Cell Signalling & Drug Discovery Research, Ewha Womans University, Seoul, South Korea
| | | | | | | | | | | |
Collapse
|
|
24
|
Murine lung eosinophil activation and chemokine production in allergic airway inflammation. Cell Mol Immunol 2010; 7:361-74. [PMID: 20622891 DOI: 10.1038/cmi.2010.31] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Eosinophils play important roles in asthma and lung infections. Murine models are widely used for assessing the functional significance and mechanistic basis for eosinophil involvements in these diseases. However, little is known about tissue eosinophils in homeostasis. In addition, little data on eosinophil chemokine production during allergic airway inflammation are available. In this study, the properties and functions of homeostatic and activated eosinophils were compared. Eosinophils from normal tissues expressed costimulation and adhesion molecules B7-1, B7-2 and ICAM-1 for Ag presentation but little major histocompatibility complex (MHC) class II, and were found to be poor stimulators of T-cell proliferation. However, these eosinophils expressed high levels of chemokine mRNA including C10, macrophage inflammatory protein (MIP)-1alpha, MIP-1gamma, MIP-2, eotaxin and monocyte chemoattractant protein-5 (MCP-5), and produced chemokine proteins. Eosinophil intracellular chemokines decreased rapidly with concomitant surface marker downregulation upon in vitro culturing consistent with piecemeal degranulation. Lung eosinophils from mice with induced allergic airway inflammation exhibited increased chemokines mRNA expression and chemokines protein production and upregulated MHC class II and CD11c expression. They were also found to be the predominant producers of the CCR1 ligands CCL6/C10 and CCL9/MIP-1gamma in inflamed lungs. Eosinophil production of C10 and MIP-1gamma correlated with the marked influx of CD11b(high) lung dendritic cells during allergic airway inflammation and the high expression of CCR1 on these dendritic cells (DCs). The study provided baseline information on tissue eosinophils, documented the upregulation of activation markers and chemokine production in activated eosinophils, and indicated that eosinophils were a key chemokine-producing cell type in allergic lung inflammation.
Collapse
|
|
25
|
Kim M, Min HJ, Won HY, Park H, Lee JC, Park HW, Chung J, Hwang ES, Lee K. Dimerization of translationally controlled tumor protein is essential for its cytokine-like activity. PLoS One 2009; 4:e6464. [PMID: 19649253 PMCID: PMC2715101 DOI: 10.1371/journal.pone.0006464] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2009] [Accepted: 06/25/2009] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND Translationally Controlled Tumor Protein (TCTP) found in nasal lavage fluids of allergic patients was named IgE-dependent histamine-releasing factor (HRF). Human recombinant HRF (HrHRF) has been recently reported to be much less effective than HRF produced from activated mononuclear cells (HRFmn). METHODS AND FINDINGS We found that only NH(2)-terminal truncated, but not C-terminal truncated, TCTP shows cytokine releasing activity compared to full-length TCTP. Interestingly, only NH(2)-terminal truncated TCTP, unlike full-length TCTP, forms dimers through intermolecular disulfide bonds. We tested the activity of dimerized full-length TCTP generated by fusing it to rabbit Fc region. The untruncated-full length protein (Fc-HrTCTP) was more active than HrTCTP in BEAS-2B cells, suggesting that dimerization of TCTP, rather than truncation, is essential for the activation of TCTP in allergic responses. We used confocal microscopy to evaluate the affinity of TCTPs to its putative receptor. We detected stronger fluorescence in the plasma membrane of BEAS-2B cells incubated with Del-N11TCTP than those incubated with rat recombinant TCTP (RrTCTP). Allergenic activity of Del-N11TCTP prompted us to see whether the NH(2)-terminal truncated TCTP can induce allergic airway inflammation in vivo. While RrTCTP had no influence on airway inflammation, Del-N11TCTP increased goblet cell hyperplasia in both lung and rhinal cavity. The dimerized protein was found in sera from allergic patients, and bronchoalveolar lavage fluids from airway inflamed mice. CONCLUSIONS Dimerization of TCTP seems to be essential for its cytokine-like activity. Our study has potential to enhance the understanding of pathogenesis of allergic disease and provide a target for allergic drug development.
Collapse
Affiliation(s)
- Miyoung Kim
- College of Pharmacy, Center for Cell Signaling Research and Drug Discovery Research, Ewha Womans University, Seoul, Korea
| | - Hyun Jung Min
- College of Pharmacy, Center for Cell Signaling Research and Drug Discovery Research, Ewha Womans University, Seoul, Korea
| | - Hee Yeon Won
- College of Pharmacy, Center for Cell Signaling Research and Drug Discovery Research, Ewha Womans University, Seoul, Korea
| | - Heejin Park
- College of Pharmacy, Center for Cell Signaling Research and Drug Discovery Research, Ewha Womans University, Seoul, Korea
| | | | - Heung-Woo Park
- Division of Allergy and Clinical Immunology, Seoul National University Hospital, Seoul, Korea
| | - Junho Chung
- College of Medicine and Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Eun Sook Hwang
- College of Pharmacy, Center for Cell Signaling Research and Drug Discovery Research, Ewha Womans University, Seoul, Korea
| | - Kyunglim Lee
- College of Pharmacy, Center for Cell Signaling Research and Drug Discovery Research, Ewha Womans University, Seoul, Korea
| |
Collapse
|
|
26
|
Mitchell A, Rentero C, Endoh Y, Hsu K, Gaus K, Geczy C, McNeil HP, Borges L, Tedla N. LILRA5 is expressed by synovial tissue macrophages in rheumatoid arthritis, selectively induces pro-inflammatory cytokines and IL-10 and is regulated by TNF-alpha, IL-10 and IFN-gamma. Eur J Immunol 2009; 38:3459-73. [PMID: 19009525 DOI: 10.1002/eji.200838415] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Leukocyte immunoglobulin-like receptor A5 (LILRA5) belongs to a family of receptors known to regulate leukocyte activation. There are two membrane-bound and two soluble forms of LILRA5. The transmembrane LILRA5 contain a short cytoplasmic domain and a charged arginine residue within the transmembrane region. Cross-linking of LILRA5 on monocytes induced production of pro-inflammatory cytokines, suggesting that LILRA5 plays a role in inflammation. However, expression of LILRA5 in diseases with extensive inflammatory component is unknown. Rheumatoid arthritis (RA) is a chronic inflammatory synovitis characterized by unregulated activation of leukocytes leading to joint destruction. Here we demonstrate extensive LILRA5 expression on synovial tissue macrophages and in synovial fluid of patients with active RA but not in patients with osteoarthritis. We also show that LILRA5 associated with the common gamma chain of the FcR and LILRA5 cross-linking induced phosphorylation of Src tyrosine kinases and Spleen tyrosine kinase (Syk). Furthermore, LILRA5 induced selective production of pro-inflammatory cytokines as well as IL-10. LILRA5 mRNA and protein expression was tightly regulated by TNF-alpha, IL-10 and IFN-gamma. Increased expression of LILRA5 in rheumatoid tissue, together with its ability to induce key cytokines involved in RA, suggests that this novel receptor may contribute to disease pathogenesis.
Collapse
Affiliation(s)
- Ainslie Mitchell
- Centre for Infection and Inflammation Research, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
| | | | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Thomas M, Edwards MJ, Sawicka E, Duggan N, Hirsch E, Wymann MP, Owen C, Trifilieff A, Walker C, Westwick J, Finan P. Essential role of phosphoinositide 3-kinase gamma in eosinophil chemotaxis within acute pulmonary inflammation. Immunology 2008; 126:413-22. [PMID: 18754810 DOI: 10.1111/j.1365-2567.2008.02908.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
We and others have established an important role for phosphoinositide-3 kinase gamma (PI3Kgamma) in the chemotactic responses of macrophages and neutrophils. The involvement of this lipid kinase in allergic inflammatory responses is, however, yet to be fully determined. Here we compare wild-type (WT) and PI3Kgamma(-/-) (KO) mice within a model of ovalbumin (OVA) -specific pulmonary inflammation. Upon OVA aerosol challenge, cell influx into the bronchoalveolar lavage (BAL) fluid consisted of neutrophils, macrophages and, more significantly, eosinophils - which are key effector cells in allergic inflammation. Each population was reduced by up to 80% in KO mice, demonstrating a role for PI3Kgamma in cell infiltration into the airways. The mechanism of reduced eosinophilia was analysed within both development and effector stages of the immune response. Comparable levels of OVA-specific T-cell proliferation and immunoglobulin production were established in both strains. Furthermore, no significant differences between WT and KO chemokine production were observed. Having identified the critical point of PI3Kgamma involvement, KO eosinophil chemotactic dysfunction was confirmed in vitro. These data are the first to demonstrate the vital role of PI3Kgamma in acute allergic inflammation. The profound dependency of eosinophils on PI3Kgamma for pulmonary influx identifies this lipid kinase as an attractive target for the pharmacological intervention of asthma.
Collapse
Affiliation(s)
- Matthew Thomas
- Novartis Institutes for BioMedical Research, Horsham, West Sussex, United Kingdom.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
28
|
Walsh GM. The anti‐inflammatory effects of the second‐generation antihistamines. Dermatol Ther 2008. [DOI: 10.1111/j.1529-8019.2000.00042.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Garry M. Walsh
- University of Aberdeen Medical School, Aberdeen, Scotland
| |
Collapse
|
|
29
|
Abstract
Hypereosinophilic syndrome (HES) is a rare disorder characterized by persistent and marked eosinophilia. Some HES forms have a poor prognosis, either because of end-organ damage (particularly endomyocardial fibrosis), or because of associated myeloid leukemia or malignant T-cell lymphoma. Oral mucosa ulcerations can be early clinical signs in severe forms. They are discrete, round or oval, sometimes confluent ulcers or erosions, located on non-keratinized, unattached oral mucosa. In the last 15 years a better understanding of eosinophil biology has led to a new clinical classification of HES. The lymphocytic form is characterized by T-lymphocyte clonality, IL-5 production, and a possible progression to T-cell lymphoma. Oral lesions are more frequently associated with the myeloproliferative form, characterized by an increased risk of developing myeloid malignancies and a good response to a recent anti-tyrosine kinase therapy (imatinib mesylate). The target of imatinib is a novel kinase resulting from an 800-kb deletion on chromosome 4. Recently, the resulting FIP1L1-PDGFRalpha fusion gene was characterized as a marker of response to imatinib. Exclusion of other erosive ulcerative oral disease and early recognition of HES in patients with oral ulcerations, and precise characterization of the lymphocytic or myeloproliferative form are therefore important to rapidly initiate an effective therapy.
Collapse
Affiliation(s)
- M A Ionescu
- Inserm U728, Université Paris VII, Hôpital Saint Louis, 1 Avenue Claude Vellefaux, 75475, Paris Cedex 10, France
| | | | | |
Collapse
|
|
30
|
DiScipio RG, Schraufstatter IU. The role of the complement anaphylatoxins in the recruitment of eosinophils. Int Immunopharmacol 2007; 7:1909-23. [PMID: 18039528 DOI: 10.1016/j.intimp.2007.07.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2007] [Accepted: 07/09/2007] [Indexed: 01/21/2023]
Abstract
Eosinophils are blood and tissue immune cells that participate in a diverse range of activities normally beneficial for the host defense, but in circumstances of untoward inflammatory conditions these cells can be responsible for pathological responses. Accordingly the transit of eosinophils from the blood to tissues is a subject of considerable importance in immunology. In this article we review how the complement anaphylatoxins, C3a and C5a bring about eosinophil extravasation. These mediators do not merely provide a chemotactic or haptotactic gradient but are responsible for orchestrating innumerable responses by other cells types, including of endothelial cells, mast cells, and basophils in order to create an environment that is conducive for eosinophil infiltration. C5a has the capacity to prime the endothelium directly to present P-selectin, and C5a stimulated generation of eosinophil hydrogen peroxide and other oxidants can cause additional upregulation of endothelial P-selectin and ICAM-1. Moreover, the anaphylatoxins have the ability to recruit mast cells and basophils and can stimulate these cells to release IL-4 and IL-13, which by augmenting endothelial VCAM-1, convey some selectivity for eosinophils. The anaphylatoxins also have the capability to evoke the release and activation of eosinophil MMP-9, which is employed by this cell type to digest its way past the subendothelial matrix. Finally, because C3a and C5a can stimulate the generation of nitric oxide along with the secretion of histamine and LTC4 from several cell types, the anaphylatoxins can bring about an increase in vascular permeability that facilitates eosinophil accumulation at sites of allergic inflammation.
Collapse
Affiliation(s)
- Richard G DiScipio
- La Jolla Institute for Molecular Medicine, 4570 Executive Dr. #100, San Diego, CA 92122, USA.
| | | |
Collapse
|
|
31
|
Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, Hippe A, Corrigan CJ, Dong C, Homey B, Yao Z, Ying S, Huston DP, Liu YJ. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. ACTA ACUST UNITED AC 2007; 204:1837-47. [PMID: 17635955 PMCID: PMC2118667 DOI: 10.1084/jem.20070406] [Citation(s) in RCA: 496] [Impact Index Per Article: 27.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Interleukin (IL) 25 (IL-17E), a distinct member of the IL-17 cytokine family, plays important roles in evoking T helper type 2 (Th2) cell–mediated inflammation that features the infiltrations of eosinophils and Th2 memory cells. However, the cellular sources, target cells, and underlying mechanisms remain elusive in humans. We demonstrate that human Th2 memory cells expressing distinctive levels of IL-25 receptor (R) are one of the responding cell types. IL-25 promotes cell expansion and Th2 cytokine production when Th2 central memory cells are stimulated with thymic stromal lymphopoietin (TSLP)–activated dendritic cells (DCs), homeostatic cytokines, or T cell receptor for antigen triggering. The enhanced functions of Th2 memory cells induced by IL-25 are associated with sustained expression of GATA-3, c-MAF, and JunB in an IL-4–independent manner. Although keratinocytes, mast cells, eosinophils, and basophils express IL-25 transcripts, activated eosinophils and basophils from normal and atopic subjects were found to secrete bioactive IL-25 protein, which augments the functions of Th2 memory cells. Elevated expression of IL-25 and IL-25R transcripts was observed in asthmatic lung tissues and atopic dermatitis skin lesions, linking their possible roles with exacerbated allergic disorders. Our results provide a plausible explanation that IL-25 produced by innate effector eosinophils and basophils may augment the allergic inflammation by enhancing the maintenance and functions of adaptive Th2 memory cells.
Collapse
Affiliation(s)
- Yui-Hsi Wang
- Department of Immunology and Center of Cancer Immunology Research, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Murat-Susić S, Lipozencić J, Zizić V, Husar K, Marinović B. Serum eosinophil cationic protein in children with atopic dermatitis. Int J Dermatol 2007; 45:1156-60. [PMID: 17040428 DOI: 10.1111/j.1365-4632.2006.02865.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Eosinophil cationic protein (ECP) is a cytotoxic agent secreted by activated eosinophils during allergic and inflammatory processes. The aim of the study was to determine the ECP level, absolute and relative eosinophil count and IgE antibodies in children with atopic dermatitis (AD) compared with those of nonatopic children, and to assess the correlation of these laboratory parameters with the clinical severity of AD. METHODS This prospective study comprised 70 children. There were 49 children with AD aged 3-36 months, and the control group comprised 21 children with a negative personal and family history for atopic diseases. Detailed history, serum ECP levels (UniCAP FEIA), relative and absolute eosinophil counts and total serum IgE antibodies were determined in both groups. In the children with AD, skin involvement was measured by the SCORAD index. RESULTS The calculated SCORAD index was between 16 and 83. IgE antibodies, relative and absolute eosinophil counts showed a significantly wider range of values and a statistically higher median (P < 0.001) in the patients with AD compared with the control group. These laboratory parameters did not correlate with the severity of AD. The serum ECP median level, in the children with AD, was 16.2 microg/L (range 3.01-65.30) compared with 5.92 microg/L (range 2.76-21.90) in the control group. Correlation of the total SCORAD index and the serum ECP levels was negative, weak (r = -0.065) and statistically not significant (P > 0.05). The same was found for the correlation of serum ECP and intensity of skin changes (r = -0.095) and serum ECP and subjective symptoms (r = -0.045). The correlation was positive, but weak and statistically not significant for the serum ECP and extent of the skin lesions (r = 0.079, P > 0.05). CONCLUSION Elevated levels of ECP, relative and absolute eosinophil counts, as well as IgE antibodies were determined in the patients with AD. As these laboratory findings did not correlate with the severity of AD, they can be considered only as additional methods in the evaluation of patients with AD.
Collapse
Affiliation(s)
- S Murat-Susić
- Department of Dermatovenerology, Zagreb University Hospital Center, Children's Hospital, Zagreb, Croatia.
| | | | | | | | | |
Collapse
|
|
33
|
Taha Y, Raab Y, Carlson M, Larsson A, Lördal M, Lööf L, Thörn M. Steroids reduce local inflammatory mediator secretion and mucosal permeability in collagenous colitis patients. World J Gastroenterol 2006; 12:7012-8. [PMID: 17109497 PMCID: PMC4087346 DOI: 10.3748/wjg.v12.i43.7012] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the effect of oral steroids upon clinical response and rectal mucosa secretion of eosinophil cationic protein (ECP), myeloperoxidase (MPO), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and albumin in patients with collagenous colitis (CC).
METHODS: A segmental perfusion technique was used to collect perfusates from rectum of CC patients once before and twice (one and four weeks) after the start of steroid treatment. Clinical data was monitored and ECP, MPO, bFGF, VEGF and albumin concentrations were analyzed by immunochemical methods in perfusates and in serum.
RESULTS: Steroids reduced the number of bowel movements by more than five times within one week and all patients reported improved subjective well-being at wk 1 and 4. At the same time, the median concentrations of ECP, bFGF, VEGF and albumin in rectal perfusates decreased significantly. MPO values were above the detection limit in only 3 patients before treatment and in none during treatment. VEGF, bFGF, ECP and albumin concentrations correlated with each other with the exception of ECP and albumin. A decrease of serum ECP and VEGF concentrations was also seen even if the overtime reduction was not significant.
CONCLUSION: Oral steroid treatment in CC patients induced a simultaneous reduction of bowel movements and rectal release of ECP, bFGF, VEGF and albumin, suggesting that these polypeptides and increased mucosal permeability are important components of the pathophysiology in collagenous colitis.
Collapse
Affiliation(s)
- Yesuf Taha
- Departments of Medical Sciences, University Hospital, Uppsala, Sweden.
| | | | | | | | | | | | | |
Collapse
|
|
34
|
Hirshberg A, Amariglio N, Akrish S, Yahalom R, Rosenbaum H, Okon E, Kaplan I. Traumatic ulcerative granuloma with stromal eosinophilia: a reactive lesion of the oral mucosa. Am J Clin Pathol 2006; 126:522-9. [PMID: 16938660 DOI: 10.1309/afha406gbt0n2y64] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a benign lesion of the oral mucosa of an unclear pathogenesis. We analyzed the profile of the inflammatory infiltrate in 12 cases of TUGSE by using immunohistochemical analysis and polymerase chain reaction-based repertoire analysis to detect T- and B-cell receptor gene rearrangements. The inflammatory infiltrate consisted in most cases of B and T lymphocytes, macrophages, abundant eosinophils, and large atypical cells. In 5 cases, CD30+ cells were found. Spectratyping analysis displayed a polyclonal rearrangement of the T-cell receptor g gene in 6 cases and oligoclonality in 5 cases. Monoclonality was observed in 1 case that also fulfilled histologic criteria for lymphoma. Healing was uneventful in all cases, including the one suspected of being lymphoma, with no recurrences in more than 2 years'follow-up. TUGSE can be regarded reactive. Some cases, however, may harbor a dominant clonal T-cell population; in these cases, long-term follow-up is mandatory.
Collapse
Affiliation(s)
- Abraham Hirshberg
- Department of Oral Pathology and Oral Medicine, Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | | | | | | | | | | |
Collapse
|
|
35
|
Werneck-Silva AL, Alvares EP, Gama P, Damião AOMC, Osaki LH, Ogias D, Sipahi AM. Intestinal damage in strongyloidiasis: the imbalance between cell death and proliferation. Dig Dis Sci 2006; 51:1063-1069. [PMID: 16865572 DOI: 10.1007/s10620-006-8010-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2005] [Accepted: 07/14/2005] [Indexed: 12/25/2022]
Abstract
Strongyloidiasis is an endemic tropical parasitosis caused by Strongyloides stercoralis that also affects immigrants in nontropical countries. The nematode colonizes the duodenum and upper jejunum, inducing mucosal alterations. Because integrity is essential for a functional barrier, we aimed to study apoptosis and proliferation in the small bowel epithelium infected with S. stercoralis. We evaluated 23 patients and 17 controls. Apoptotic cells were detected by TUNEL and M30 immunolabelling, whereas proliferation was scored by Ki67 immunostaining and mitotic counting. Infection increased apoptotic indices in duodenum and jejunum (P < 0.001). Conversely, it decreased cell proliferation in both segments (P < 0.001). Our results showed that intestinal strongyloidiasis promotes an imbalance between cell death and proliferation. This is the first evidence of disruption of the epithelial kinetics with S. stercoralis infection, though the mechanisms remain unclear. Furthermore, our results support the idea that strongyloidiasis disturbs the mucosal integrity and can compromise the intestinal barrier.
Collapse
Affiliation(s)
- Ana Luiza Werneck-Silva
- Department of Gastroenterology, School of Medicine, Laboratory of Investigation (LIM 07), University of São Paulo, São Paulo, Brazil
| | | | | | | | | | | | | |
Collapse
|
|
36
|
|
|
37
|
KARPPINEN A, RANTALA I, VAALASTI A, PALOSUO T, REUNALA T. Effect of cetirizine on the inflammatory cells in mosquito bites. Clin Exp Allergy 2006. [DOI: 10.1111/j.1365-2222.1996.tb00597.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
|
|
38
|
MAESTRELLI P, OCCARI P, TURATO G, PAPIRIS SA, DI STEEANO A, MAPP CE, MILANI GF, EABBRI LM, SAETTA M. Expression of interleukin (IL)-4 and IL-5 proteins in asthma induced by toluene diisocyanate (TDI). Clin Exp Allergy 2006. [DOI: 10.1111/j.1365-2222.1997.tb01174.x] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
|
|
39
|
Harada M, Kumemura H, Yanagimoto C, Sata M. Vascular endothelial growth factor is involved in angioedema associated with eosinophilia. Kurume Med J 2006; 52:89-91. [PMID: 16422174 DOI: 10.2739/kurumemedj.52.89] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Angioedema associated with eosinophilia is a disorder characterized by angioedema and eosinophilia. However, the pathogenesis of this disorder has not been fully understood. We experienced 4 patients with angioedema associated with eosinophilia. All patients were young, 3 were female and 1 was male. All patients revealed edema of the limbs and eosinophilia. The symptom was rapidly improved after the initiation of low or medium dose of prednisolone. We evaluated the serum concentration of interleukin 5 (IL-5) and the plasma concentration of vascular endothelial growth factor (VEGF) in 1 patient. Both cytokines were markedly elevated before the treatment and decreased after the treatment. Angioedema associated with eosinophilia is not so rare, and IL-5 and VEGF are involved in the pathogenesis of this disease.
Collapse
Affiliation(s)
- Masaru Harada
- Department of Medicine, Kurume University School of Medicine and Research Center for Innovative Cancer Therapy of the 21st Century COE Program for Medical Science, Kurume University, Kurume 830-0011, Japan
| | | | | | | |
Collapse
|
|
40
|
Ozdemir BH, Ozdemir FN, Demirhan B, Haberal M. TGF-β1 Expression in Renal Allograft Rejection and Cyclosporine A Toxicity. Transplantation 2005; 80:1681-5. [PMID: 16378061 DOI: 10.1097/01.tp.0000185303.92981.d6] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND To assess short- and long-term influence of the TGF-beta1 on renal allografts. METHODS Expression of TGF-beta1 and TNF-alpha, and the proportion of macrophages and eosinophils in interstitium were evaluated in 64 cases including five cases with nonrejected kidneys (NRK), 18 cases with acute rejection (AR), 26 cases with chronic allograft nephropathy (CAN), and 15 cases with acute cyclosporine A (CsA) toxicity. Follow-up biopsies of all cases with AR and CsA toxicity were evaluated for development of interstitial fibrosis (IF) and graft atherosclerosis (GAS). Additionally, influence of tubular-TGF-beta1 expression on graft function during 6 months after the diagnostic biopsy was evaluated. RESULTS A significant differences was seen between rejected kidneys and acute CsA toxicity in regards of tubular TGF-beta1 expression that patients with CsA toxicity exhibited significantly higher grade of tubular TGF-beta1 expression than patients with AR (P<0.05) and CAN (P<0.05). A significant difference was found between the grades of tubular TGF-beta1 expression in regards to graft function of cases with AR and CsA toxicity (P<0.05). Higher grade tubular TGF-beta1 expression showed better graft function during 6 months. Besides the degree of renal TGF-beta1 expression was positively correlated with development of diffuse IF and GAS (P<0.05) that the risk of the IF and GAS was higher in cases with grade 2 renal TGF-beta1 expression. CONCLUSIONS Despite the short-term posttransplantation tubule-repairing effects of TGF-beta1, the overall effects of TGF-beta1 in the kidney seem to be negative that increased expression of TGF-beta1 promotes IF and vasculopathy associated with CAN.
Collapse
Affiliation(s)
- B Handan Ozdemir
- Department of Pathology, Baskent University Faculty of Medicine, Ankara, Turkey.
| | | | | | | |
Collapse
|
|
41
|
Straumann A, Kristl J, Conus S, Vassina E, Spichtin HP, Beglinger C, Simon HU. Cytokine expression in healthy and inflamed mucosa: probing the role of eosinophils in the digestive tract. Inflamm Bowel Dis 2005; 11:720-6. [PMID: 16043986 DOI: 10.1097/01.mib.0000172557.39767.53] [Citation(s) in RCA: 101] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND In eosinophilic esophagitis (EE), the esophagus is infiltrated with activated eosinophils that often evoke tissue damage, but the intestines of these patients remain unaffected. We thus hypothesized that different tissue-dwelling eosinophil populations may coexist: activated eosinophils that infiltrate the esophagus and resting eosinophils that reside in unaffected intestines. We sought to characterize different eosinophil subpopulations by comparing the expression of certain proinflammatory proteins in tissue-dwelling eosinophils at different parts of the gastrointestinal tract. METHODS The 8 patients participating included 6 men and 2 women with a previously confirmed diagnosis of EE, whose average age was 39.4 years (range, 20-55 yr) and average disease duration was 13.6 years (range, 2-26 yr). Controls were 3 men and 1 woman, with a mean age of 43.3 years (range, 29-56 yr) with untreated functional dyspepsia who underwent diagnostic esophagogastroduodenoscopy. Six additional individuals having normal blood eosinophils were recruited for cytokine measurements in blood eosinophils. Immunofluorescence and immunoassays charted expression of CD25 and the TH2 cytokines, interleukin (IL)-4, IL-5, IL-10, and IL-13, in esophageal, intestinal, and blood eosinophils from controls and patients. RESULTS Controls showed a small but significant proportion of intestinal, but no blood, eosinophils expressing CD25 and IL-13, suggesting physiologic activation occurring in the digestive tract. On the other hand, eosinophils infiltrating the inflamed esophageal mucosa of patients with EE showed strong evidence of activation, with most expressing CD25, IL-4, and IL-13. Moreover, IL-13-positive intestinal eosinophils were increased in patients compared with controls. CONCLUSIONS We thus conclude that tissue-dwelling eosinophils show different and distinct cytokine expression patterns under noninflammatory and inflammatory conditions.
Collapse
Affiliation(s)
- Alex Straumann
- Department of Gastroenterology, Kantonsspital, Olten, Switzerland.
| | | | | | | | | | | | | |
Collapse
|
|
42
|
Yoon SW, Kim TY, Sung MH, Kim CJ, Poo H. Comparative proteomic analysis of peripheral blood eosinophils from healthy donors and atopic dermatitis patients with eosinophilia. Proteomics 2005; 5:1987-95. [PMID: 15832365 DOI: 10.1002/pmic.200401086] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Atopic dermatitis (AD) is an allergic disease that has recently shown a dramatic increase of incidence in developed countries. Eosinophilia, the accumulation of eosinophils, occurs in AD patients through an anti-apoptotic mechanism. To understand the target proteins involved in the anti-apoptotic signaling of eosinophilia, we used a proteomic approach to analyze eosinophil proteins from AD patients with eosinophilia and healthy donors. Protein spots in two-dimensional electrophoresis (2-DE) gels were identified with peptide mass fingerprinting (PMF) based on matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and database searching. More spots were observed in the 2-DE proteome map from AD patient samples (1310 +/- 58 spots) than in those from healthy donors (1121 +/- 40 spots). We identified 51 proteins affected by eosinophilia: 19 related to signaling, 8 involved in regulation of metabolism, 4 related to apoptosis, and 3 involved in inflammation. The other identified proteins were associated with transcription, RNA processing, translation, the cytoskeleton, and unknown functions. Among the identified proteins, we observed prominent increases in the expressions of cyclinA2, voltage-dependent anion channel protein 2, and 38 kDa FK506 binding protein 8 in eosinophils from AD patients in comparison to healthy donors. PMF and immunoblotting of a single spot that was expressed in eosinophils from healthy individuals but not in AD patients identified the protein as phosphorylated growth receptor binding 7 (Grb7) adaptor protein. Increased phosphorylation of Grb7 and its upstream signaling protein, focal adhesion kinase (FAK), was detected in low viability eosinophils such as those from healthy donors or in cultured eosinophils (AML14.3D10 cells) treated with dexamethasone. These results suggest that phosphorylation of Grb7 and the expressions of cyclinA2, voltage-dependent anion channel protein 2, and 38 kDa FK506 binding protein 8 may be related with the anti-apoptosis mechanism of eosinophilia.
Collapse
Affiliation(s)
- Sun Woo Yoon
- System Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon
| | | | | | | | | |
Collapse
|
|
43
|
Lampinen M, Carlson M, Håkansson LD, Venge P. Cytokine-regulated accumulation of eosinophils in inflammatory disease. Allergy 2004; 59:793-805. [PMID: 15230810 DOI: 10.1111/j.1398-9995.2004.00469.x] [Citation(s) in RCA: 249] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The role of cytokines in the accumulation of eosinophil granulocytes in inflamed tissue has been studied extensively during recent years, and these molecules have been found to participate throughout the whole process of eosinophil recruitment. Haematopoietic cytokines such as IL-3, IL-5 and GM-CSF stimulate the proliferation and differentiation of eosinophils in the bone marrow, and the release of mature eosinophils from the bone marrow into the blood is probably promoted by IL-5. Priming of eosinophils in the blood following, for example, allergen challenge is performed mainly by IL-3, IL-5 and GM-CSF. An important step in the extravasation of eosinophils is their adhesion to the vascular endothelium. Adhesion molecules are upregulated by, e.g. IL-1, IL-4, TNF-alpha and IFN-gamma and the same cytokines may also increase the affinity of adhesion molecules both on eosinophils and endothelial cells. Finally, a number of cytokines have been shown to act as eosinophil chemotactic factors, attracting the cells to the inflammatory focus in the tissue. Some of the most important eosinophil chemoattractant cytokines are IL-5, IL-8, RANTES, eotaxin, eotaxin-2, eotaxin-3, MCP-3, MCP-4 and TNF-alpha. Th2 cells, mast cells and epithelial cells are important sources of proinflammatory cytokines, but in recent years, the eosinophils have also been recognized as cytokine-producing and thereby immunoregulatory cells. The aim of this paper is to review the role of cytokines in the process of eosinophil recruitment in asthma, allergy and ulcerative colitis.
Collapse
Affiliation(s)
- M Lampinen
- Asthma Research Centre, Department of Medical Sciences, Clinical Chemistry, University Hospital, S-751 85 Uppsala, Sweden
| | | | | | | |
Collapse
|
|
44
|
Copeland BH, Aramide OO, Wehbe SA, Fitzgerald SM, Krishnaswamy G. Eosinophilia in a patient with cyclical vomiting: a case report. Clin Mol Allergy 2004; 2:7. [PMID: 15144561 PMCID: PMC425596 DOI: 10.1186/1476-7961-2-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2003] [Accepted: 05/14/2004] [Indexed: 02/08/2023] Open
Abstract
Background Eosinophilic gastritis is related to eosinophilic gastroenteritis, varying only in regards to the extent of disease and small bowel involvement. Common symptoms reported are similar to our patient's including: abdominal pain, epigastric pain, anorexia, bloating, weight loss, diarrhea, ankle edema, dysphagia, melaena and postprandial nausea and vomiting. Microscopic features of eosinophilic infiltration usually occur in the lamina propria or submucosa with perivascular aggregates. The disease is likely mediated by eosinophils activated by various cytokines and chemokines. Therapy centers around the use of immunosuppressive agents and dietary therapy if food allergy is a factor. Case presentation The patient is a 31 year old Caucasian female with a past medical history significant for ulcerative colitis. She presented with recurrent bouts of vomiting, abdominal pain and chest discomfort of 11 months duration. The bouts of vomiting had been reoccurring every 7–10 days, with each episode lasting for 1–3 days. This was associated with extreme weakness and cachexia. Gastric biopsies revealed intense eosinophilic infiltration. The patient responded to glucocorticoids and azathioprine. The differential diagnosis and molecular pathogenesis of eosinophilic gastritis as well as the molecular effects of glucocorticoids in eosinophilic disorders are discussed. Conclusions The patient responded to a combination of glucocorticosteroids and azathioprine with decreased eosinophilia and symptoms. It is likely that eosinophil-active cytokines such as interleukin-3 (IL-3), granulocyte macrophage colony stimulating factor (GM-CSF) and IL-5 play pivotal roles in this disease. Chemokines such as eotaxin may be involved in eosinophil recruitment. These mediators are downregulated or inhibited by the use of immunosuppressive medications.
Collapse
Affiliation(s)
- Billy H Copeland
- P.O. Box 70622, Department of Internal Medicine, Division of Allergy and Immunology, East Tennessee State University, Johnson City, TN 37614, USA
| | - Omolola O Aramide
- P.O. Box 70622, Department of Internal Medicine, Division of Allergy and Immunology, East Tennessee State University, Johnson City, TN 37614, USA
| | - Salim A Wehbe
- P.O. Box 70622, Department of Internal Medicine, Division of Allergy and Immunology, East Tennessee State University, Johnson City, TN 37614, USA
| | - S Matthew Fitzgerald
- P.O. Box 70622, Department of Internal Medicine, Division of Allergy and Immunology, East Tennessee State University, Johnson City, TN 37614, USA
| | - Guha Krishnaswamy
- P.O. Box 70622, Department of Internal Medicine, Division of Allergy and Immunology, East Tennessee State University, Johnson City, TN 37614, USA
| |
Collapse
|
|
45
|
Dahlman-Ghozlan K, Ortonne JP, Heilborn JD, Stephansson E. Altered tissue expression pattern of cell adhesion molecules, ICAM-1, E-selectin and VCAM-1, in bullous pemphigoid during methotrexate therapy. Exp Dermatol 2004; 13:65-9. [PMID: 15009098 DOI: 10.1111/j.0906-6705.2004.00113.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Little is known about how eosinophils accumulate in bullous pemphigoid (BP) and why these cells rapidly disappear during immunosuppressive therapy. Eosinophils can produce cytokines such as IL-4, IL-5, IL-6, IL-10 and IL13, which can induce endothelial cells to express cellular adhesion molecules (CAMs) such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) necessary for the recruitment of eosinophils from the bloodstream to the skin. The present aim was to investigate the cellular expression of these three CAMs in serial biopsies before and during oral low-dose methotrexate therapy. Seventy-four biopsy specimens, 37 from active lesions and 37 from normal skin, were taken at different intervals from eight patients with bullous pemphigoid and stained immunohistochemically with specific monoclonal antibodies for these three CAMs. The expression and distribution of CAMs in the biopsies was evaluated and scored with light-microscopic examination. The basal keratinocytes in active lesions expressed ICAM-1. A strong VCAM-1 expression of endothelial cells and pericytes was correlated to a perivascular inflammatory cell infiltrate that also showed intense immunoreactivity to ICAM-1. Endothelial cell/pericytes also expressed E-selectin strongly in the BP patients before therapy. The expression of CAMs faded during therapy and, to the best of our knowledge, this has not been previously reported. Thus we suggest that the rapid reduction of tissue eosinophils may reflect the altered pattern of cell adhesion molecules during immunosuppressive therapy, which could explain the prompt clinical improvement seen in BP patients treated with methotrexate.
Collapse
|
|
46
|
Straumann A, Simon HU. The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract. Allergy 2004; 59:15-25. [PMID: 14674928 DOI: 10.1046/j.1398-9995.2003.00382.x] [Citation(s) in RCA: 79] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Eosinophils and the gastrointestinal tract interact in an intimate and enigmatic relationship. Under healthy conditions, the presence of eosinophils is limited almost exclusively to the digestive tract mucosa where they exert several effector and immunoregulatory functions. While their precise function in the gastrointestinal tract is not completely understood, it is likely that, together with different T cell subsets, eosinophils are involved in maintaining the immunologic homeostastis across the mucosal barrier under resting conditions. Eosinophils also play a role in several inflammatory conditions, such as intestinal infections, hypersensitivity reactions, primary eosinophilic inflammations and several other chronic intestinal disorders. Depending on the responsible trigger, their effects may be beneficial or detrimental. Here, we discuss the available information regarding the physiological and pathological functions of eosinophils within the gastrointestinal tract.
Collapse
Affiliation(s)
- A Straumann
- Department of Gastroenterology, Kantonsspital Olten, Olten, Switzerland
| | | |
Collapse
|
|
47
|
Spriewald BM, Ensminger SM, Billing JS, Morris PJ, Wood KJ. Increased expression of transforming growth factor-β and eosinophil infiltration is associated with the development of transplant arteriosclerosis in long-term surviving cardiac allografts. Transplantation 2003; 76:1105-11. [PMID: 14557761 DOI: 10.1097/01.tp.0000076467.83192.42] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Transplant arteriosclerosis is a major limiting factor for long-term function of allografts in clinical transplantation. This study investigated the impact of three different protocols capable of inducing long-term allograft survival on the development of transplant arteriosclerosis and immune response in cardiac allografts. METHODS CBA.Ca (H2k) recipients of fully allogeneic C57/BL10 (H2b) heart grafts received a short-term course of anti-CD154 antibody or were pretreated with anti-CD4 antibody in combination with donor alloantigen in the form of CBK (H2k+Kb) bone marrow or C57BL/10 donor-specific transfusion (DST). Grafts were analyzed on day 40 or 100 after transplantation for transplant arteriosclerosis and expression of interferon-gamma, interleukin (IL)-2, IL-4, IL-10, IL-12p40, inducible nitric oxide synthase, and transforming growth factor (TGF)-beta1 mRNA. Serum was analyzed for the presence of alloantibodies. RESULTS Intimal proliferation was 62%+/-11% on day 40 in the anti-CD154 group, progressed from 31%+/-10% on day 40 to 68%+/-8% on day 100 in the CBK-bone marrow group, but remained stable at 39%+/-4% in the DST group. Increased transplant arteriosclerosis on day 100 was associated with high intragraft TGF-beta1 mRNA production and eosinophil infiltration, but not alloantibody production. Progressing transplant arteriosclerosis was associated with increased IL-4 expression. CONCLUSION Treatment protocols for the induction of long-term allograft survival can differ substantially in the extent and kinetics of transplant arteriosclerosis. IL-4 and TGF-beta1 may be two potential therapeutic targets to attenuate the development of transplant arteriosclerosis in the long term.
Collapse
Affiliation(s)
- Bernd M Spriewald
- Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, United Kingdom
| | | | | | | | | |
Collapse
|
|
48
|
Toyoda M, Nakamura M, Makino T, Morohashi M. Localization and content of nerve growth factor in peripheral blood eosinophils of atopic dermatitis patients. Clin Exp Allergy 2003; 33:950-5. [PMID: 12859452 DOI: 10.1046/j.1365-2222.2003.01719.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Atopic dermatitis (AD) is a chronic and relapsing eczematous skin disorder characterized by eosinophilia. Nerve growth factor (NGF) modulates the allergic response through interactions with immune-inflammatory cells. Eosinophils have been reported to store NGF as a preformed mediator. OBJECTIVE To gain further insight into the significance of eosinophils in association with NGF in the pathogenesis of AD, the localization of NGF within eosinophils and the difference of the eosinophil-derived NGF content in the peripheral blood of normal volunteers vs. AD patients were investigated. METHODS We examined the localization of NGF within human eosinophils using the post-embedding immunoelectron microscopy and compared NGF content in freshly isolated eosinophil sonicates from the peripheral blood of 31 normal volunteers vs. 42 AD patients by immunoenzymatic assay. A possible correlation between the levels of NGF and major basic protein was also examined. RESULTS Immunoelectron microscopic studies revealed that NGF was localized in the central core of normal eosinophil granules, where major basic protein is also present as a preformed mediator, in homogeneous granules and in intergranular ductal or vesicular structures adjacent to specific granules of eosinophils. NGF content in eosinophils was significantly increased in AD patients. Furthermore, there was a significant correlation between levels of NGF and major basic protein in eosinophils of AD patients. CONCLUSIONS Increased levels of NGF contained in eosinophils of the peripheral blood from AD patients, when released with other mediators such as basic proteins, could promote inflammation and local tissue damage.
Collapse
Affiliation(s)
- M Toyoda
- Department of Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan.
| | | | | | | |
Collapse
|
|
49
|
Temkin V, Kantor B, Weg V, Hartman ML, Levi-Schaffer F. Tryptase activates the mitogen-activated protein kinase/activator protein-1 pathway in human peripheral blood eosinophils, causing cytokine production and release. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2002; 169:2662-9. [PMID: 12193739 DOI: 10.4049/jimmunol.169.5.2662] [Citation(s) in RCA: 91] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
We have previously shown that mast cells enhance eosinophil survival and activation. In this study we further characterized mast cell activity toward eosinophils. Sonicate of both rat peritoneal mast cells and the human mast cell line 1 (HMC-1) induced a concentration-dependent IL-6 and IL-8 release from human peripheral blood eosinophils (ELISA). HMC-1-induced IL-8 release was significantly reduced by the tryptase inhibitors GW-45 and GW-58 (90 and 87%, respectively, at an optimal concentration) but not by anti-stem cell factor, anti-TNF-alpha, or anti-IFN-gamma neutralizing Abs or by the antihistamine drugs pyrilamine and cimetidine. In a manner similar to HMC-1, human recombinant tryptase induced the expression of mRNA for IL-8 (RT-PCR) and caused IL-8 release from the eosinophils. Addition of cycloheximide, actinomycin D, dexamethasone, PD 98059, curcumin, or SB 202190 completely inhibited the tryptase-induced IL-6 and IL-8 release. In contrast, cyclosporin A had no effect on tryptase-induced IL-8 release. Tryptase caused phosphorylation of extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinases 1 and 2, and p38 (Western blot). Tryptase also induced the translocation of c-Jun from the cytosol to the nucleus (confocal microscopy) and enhanced AP-1 binding activity to the DNA (EMSA). Eosinophils were found to express proteinase-activated receptor 2 (FACS). When eosinophils were incubated with tryptase in the presence of anti-proteinase-activated receptor 2 antagonist Abs a significant decrease in the IL-6 and IL-8 release occurred. In summary, we have demonstrated that the preformed mast cell mediator tryptase induces cytokine production and release in human peripheral blood eosinophils by the mitogen-activated protein kinase/AP-1 pathway.
Collapse
Affiliation(s)
- Vladislav Temkin
- Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel
| | | | | | | | | |
Collapse
|
|
50
|
Schmid-Grendelmeier P, Altznauer F, Fischer B, Bizer C, Straumann A, Menz G, Blaser K, Wüthrich B, Simon HU. Eosinophils express functional IL-13 in eosinophilic inflammatory diseases. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2002; 169:1021-7. [PMID: 12097410 DOI: 10.4049/jimmunol.169.2.1021] [Citation(s) in RCA: 185] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
IL-13 is an immunoregulatory and effector cytokine in allergic diseases such as bronchial asthma. A variety of immune and non-immune cells are known as IL-13 producers. In this study we investigated whether and under what conditions human eosinophils generate IL-13. Freshly isolated highly purified peripheral blood eosinophils from patients with several eosinophilic inflammatory diseases and from normal control individuals were investigated. We observed that blood eosinophils from patients suffering from bronchial asthma, atopic dermatitis, parasitic infections, hypereosinophilic syndrome, and idiopathic eosinophilic esophagitis expressed IL-13, as assessed by ELISA, ELISPOT assay, flow cytometry, and immunocytochemistry. By using nasal polyp tissues and immunohistochemistry, we demonstrated IL-13 expression in eosinophils under in vivo conditions. In contrast, blood eosinophils from control individuals as well as blood neutrophils from both eosinophilic and control patients did not produce detectable IL-13 levels. However, when blood eosinophils from control individuals were stimulated with GM-CSF or IL-5 in vitro, they generated IL-13 mRNA and protein, suggesting that IL-13 expression by eosinophils under inflammatory conditions is a cytokine-driven process. Stimulation of blood eosinophils containing IL-13 by eotaxin resulted in a rapid release of this cytokine. Eosinophil-derived IL-13 was functional, as it increased the surface expression of the low affinity IgE receptor (CD23) on purified B cells. In conclusion, human eosinophils are able to produce and release functional IL-13 in eosinophilic inflammatory responses.
Collapse
|