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Jiménez-Cortegana C, Palomares F, Alba G, Santa-María C, de la Cruz-Merino L, Sánchez-Margalet V, López-Enríquez S. Dendritic cells: the yin and yang in disease progression. Front Immunol 2024; 14:1321051. [PMID: 38239364 PMCID: PMC10794555 DOI: 10.3389/fimmu.2023.1321051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 12/12/2023] [Indexed: 01/22/2024] Open
Abstract
Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and originate favorable immune responses in many diseases, such as cancer. However, in the last decades, it has been observed that DCs not only promote beneficial responses, but also drive the initiation and progression of some pathologies, including inflammatory bowel disease (IBD). In line with those notions, different therapeutic approaches have been tested to enhance or impair the concentration and role of the different DC subsets. The blockade of inhibitory pathways to promote DCs or DC-based vaccines have been successfully assessed in cancer, whereas the targeting of DCs to inhibit their functionality has proved to be favorable in IBD. In this review, we (a) described the general role of DCs, (b) explained the DC subsets and their role in immunogenicity, (c) analyzed the role of DCs in cancer and therapeutic approaches to promote immunogenic DCs and (d) analyzed the role of DCs in IBD and therapeutic approaches to reduced DC-induced inflammation. Therefore, we aimed to highlight the "yin-yang" role of DCs to improve the understand of this type of cells in disease progression.
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Affiliation(s)
- Carlos Jiménez-Cortegana
- Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Seville, Seville, Spain
| | - Francisca Palomares
- Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Seville, Seville, Spain
| | - Gonzalo Alba
- Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Seville, Seville, Spain
| | - Consuelo Santa-María
- Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Seville, Seville, Spain
| | - Luis de la Cruz-Merino
- Clinical Oncology Dept. Medicine Department, University of Seville, Virgen Macarena University Hospital, Seville, Spain
| | - Victor Sánchez-Margalet
- Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Seville, Seville, Spain
| | - Soledad López-Enríquez
- Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Seville, Seville, Spain
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Kakimoto K, Matsuura M, Fukuchi T, Hongo H, Kimura T, Aoyama N, Okuda Y, Aomatsu K, Kamata N, Yokoyama Y, Mizuno C, Inoue T, Miyazaki T, Nakamura S, Higuchi K, Nakase H. Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial. CROHNS & COLITIS 360 2020; 2:otaa073. [PMID: 34192247 PMCID: PMC7797742 DOI: 10.1093/crocol/otaa073] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Indexed: 12/20/2022]
Abstract
Background Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. Methods We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. Results The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. Conclusions GMA shows effectiveness in inducing remission in UC patients not receiving steroid. EXPECT study demonstrates that granulocyte and monocyte adsorptive apheresis has promising effectiveness with regard to inducing remission in patients with active ulcerative colitis (UC) who are not receiving steroid treatment. The first episode of UC was an independent predictor of a response in multiple logistic regression.
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Affiliation(s)
- Kazuki Kakimoto
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Takumi Fukuchi
- Department of Gastroenterology and Hepatology, Iseikai Hospital, Osaka, Osaka, Japan
| | - Hitoshi Hongo
- Department of Gastroenterology, Fujita Gastroenterological Hospital, Takatsuki, Osaka, Japan
| | - Tsuguhiro Kimura
- Department of Gastroenterology, Fujita Gastroenterological Hospital, Takatsuki, Osaka, Japan
| | - Nobuo Aoyama
- Department of Gastroenterology, Gastrointestinal Endoscopy and IBD Center, Aoyama Medical Clinic, Kobe, Hyogo, Japan
| | - Yorihide Okuda
- Department of Gastroenterology, Otemae Hospital, Osaka, Osaka, Japan
| | - Kazuki Aomatsu
- Department of Gastroenterology, Izumiotsu Municipal Hospital, Izumiotsu, Osaka, Japan
| | - Noriko Kamata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Yoko Yokoyama
- Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Chiemi Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Osaka, Japan
| | - Takuya Inoue
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Takako Miyazaki
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Shiro Nakamura
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Kazuhide Higuchi
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan
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Chen XL, Mao JW, Wang YD. Selective granulocyte and monocyte apheresis in inflammatory bowel disease: Its past, present and future. World J Gastrointest Pathophysiol 2020; 11:43-56. [PMID: 32435521 PMCID: PMC7226913 DOI: 10.4291/wjgp.v11.i3.43] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/05/2020] [Accepted: 04/09/2020] [Indexed: 02/06/2023] Open
Abstract
The etiology and pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, are not fully understood so far. Therefore, IBD still remains incurable despite the fact that significant progress has been achieved in recent years in its treatment with innovative medicine. About 20 years ago, selective granulocyte and monocyte apheresis (GMA) was invented in Japan and later approved by the Japanese health authority for IBD treatment. From then on this technique was extensively used for IBD patients in Japan and later in Europe. Clinical trials from Japan and European countries have verified the effectiveness and safety of GMA therapy in patients with IBD. In 2013, GMA therapy was approved by China State Food and Drug Administration for therapeutic use for the Chinese IBD patients. However, GMA therapy has not been extensively used in China, although a few clinical studies also showed that it was effective in clinical and endoscopic induction of remission in Chinese IBD patients with a high safety profile. This article reviews past history, present clinical application as well as the future prospective of GMA therapy for patients with IBD.
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Affiliation(s)
- Xiu-Li Chen
- Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Jing-Wei Mao
- Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Ying-De Wang
- Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
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Worel N, Mansouri Taleghani B, Strasser E. Recommendations for Therapeutic Apheresis by the Section "Preparative and Therapeutic Hemapheresis" of the German Society for Transfusion Medicine and Immunohematology. Transfus Med Hemother 2020; 46:394-406. [PMID: 31933569 DOI: 10.1159/000503937] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/07/2019] [Indexed: 01/18/2023] Open
Abstract
The section "Preparative and Therapeutic Hemapheresis" of the German Society for Transfusion Medicine and Immunohematology (DGTI) has reviewed the actual literature and updated techniques and indications for evidence-based use of therapeutic apheresis in human disease. The recommendations are mostly in line with the "Guidelines on the Use of Therapeutic Apheresis in Clinical Practice" published by the Writing Committee of the American Society for Apheresis (ASFA) and have been conducted by experts from the DACH (Germany, Austria, Switzerland) region.
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Affiliation(s)
- Nina Worel
- Department for Blood Group Serology and Transfusion Medicine, Medical University Vienna, Vienna, Austria
| | - Behrouz Mansouri Taleghani
- University Clinic of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Bern University Hospital, Inselspital, Bern, Switzerland
| | - Erwin Strasser
- Department of Transfusion Medicine and Hemostasis, University Hospital Erlangen, Erlangen, Germany
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Contini P, Negrini S, Bodini G, Trucchi C, Ubezio G, Strada P, Savarino V, Ghio M. Granulocytes and monocytes apheresis induces upregulation of TGFβ 1 in patients with active ulcerative colitis: A possible involvement of soluble HLA-I. J Clin Apher 2016; 32:49-55. [PMID: 27080173 DOI: 10.1002/jca.21466] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Revised: 02/22/2016] [Accepted: 03/28/2016] [Indexed: 12/20/2022]
Abstract
Granulocyte and monocyte apheresis has been used in different immune-mediated disorders, mainly inflammatory bowel diseases. The removal of activated leukocytes and several additional immunomodulatory mechanisms have been so far suggested to explain the anti-inflammatory effects of the treatment. Recent data indicate that, during centrifugation based apheresis, sHLA-I adsorbed to plastic circuits is able to induce TGFβ1 production in activated leukocytes. On these bases, the present study was aimed at analyzing if this model could be applied to a noncentrifugation based apheresis, such as granulocyte and monocyte apheresis. Ten patients with ulcerative colitis were enrolled. Every patient received 5 weekly apheresis treatments. Cellulose acetate beads removed from the column post-GMA were stained by fluorescent anticlass I mAb and examined by fluorescent microscope. Moreover, sFasL plasma concentration, TGFβ1 plasma levels, and the percentage of TGFβ1 positive neutrophils were evaluated before and immediately after each single apheresis. Immunofluorescent images revealed a homogeneous layer of a sHLA-I adsorbed to the surface of the beads recovered following the procedure. sFasL plasma concentration progressively increased both following the procedures and during inter-procedure periods. Consistently, also TGFβ1 plasma levels and the percentage of TGFβ1 positive neutrophils increased during the procedures with a meaningful relationship with sFasL plasma levels. Taken together, these findings suggest that the immunosuppressive effects attributed to granulocyte and monocyte apheresis might depend, at least in part, on the sensitivity of activated leucocytes to the bioactivity of sHLA-I molecules. J. Clin. Apheresis 32:49-55, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Paola Contini
- Department of Internal Medicine, I.R.C.C.S. "a.O.U. San Martino-IST" and University of Genoa, Genova, Italy
| | - Simone Negrini
- Department of Internal Medicine, I.R.C.C.S. "a.O.U. San Martino-IST" and University of Genoa, Genova, Italy
| | - Giorgia Bodini
- Department of Internal Medicine, Gastroenterology Unit I.R.C.C.S. "a.O.U. San Martino-IST" and University of Genoa, Genova, Italy
| | - Cecilia Trucchi
- Department of Health Sciences, I.R.C.C.S. "a.O.U. San Martino-IST" and University of Genoa, Genova, Italy
| | - Gianluca Ubezio
- Immunohematology and Transfusion Centre, I.R.C.C.S. "a.O.U. San Martino-IST" and University of Genoa, Genova, Italy
| | - Paolo Strada
- Immunohematology and Transfusion Centre, I.R.C.C.S. "a.O.U. San Martino-IST" and University of Genoa, Genova, Italy
| | - Vincenzo Savarino
- Department of Internal Medicine, Gastroenterology Unit I.R.C.C.S. "a.O.U. San Martino-IST" and University of Genoa, Genova, Italy
| | - Massimo Ghio
- Department of Internal Medicine, I.R.C.C.S. "a.O.U. San Martino-IST" and University of Genoa, Genova, Italy
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Leitner GC, Vogelsang H. Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults. World J Gastrointest Pharmacol Ther 2016; 7:5-20. [PMID: 26855808 PMCID: PMC4734954 DOI: 10.4292/wjgpt.v7.i1.5] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 12/14/2015] [Accepted: 01/08/2016] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.
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Ramlow W, Waitz G, Sparmann G, Prophet H, Bodammer P, Emmrich J. First Human Application of a Novel Adsorptive-Type Cytapheresis Module in Patients With Active Ulcerative Colitis: A Pilot Study. Ther Apher Dial 2013; 17:339-47. [DOI: 10.1111/1744-9987.12007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
| | | | | | | | - Peggy Bodammer
- Division of Gastroenterology; University of Rostock; Rostock; Germany
| | - Jörg Emmrich
- Division of Gastroenterology; University of Rostock; Rostock; Germany
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Vecchi M, Vernia P, Riegler G, D'Incà R, Annese V, Bagnoli S. Therapeutic landscape for ulcerative colitis: where is the Adacolumn(®) system and where should it be? Clin Exp Gastroenterol 2013; 6:1-7. [PMID: 23323022 PMCID: PMC3541711 DOI: 10.2147/ceg.s33275] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Granulocyte-monocyte apheresis is a relatively new therapy that has been proposed, sometimes with controversial results, for the treatment of inflammatory bowel disease, particularly ulcerative colitis. The aim of the present study was to perform a thorough review of the literature on the application of this type of treatment in ulcerative colitis and discuss the results, in order to provide an opinion on its use which is shared by the involved experts. The review of the literature was performed by searching PubMed with appropriate key words. The results obtained suggest that the major role for this treatment at this moment is for those patients with steroid dependency or with major contraindications to use of steroids. However, promising, albeit very preliminary, results have also been observed in steroid-naïve subjects, and this is of particular interest in consideration of the safety profile of this therapeutic method. As such, the Adacolumn may prove useful in specific subgroups of patients. Future phenotypic, genotypic, and molecular characterization of patients with inflammatory bowel disease might prove useful in defining better those subjects who might benefit most from this treatment modality.
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Affiliation(s)
- Maurizio Vecchi
- University of Milan, Department of Biomedical Sciences for Health, San Donato Milanese, Milan
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Fujisawa T, Murase K, Kanoh H, Takemura M, Ohnishi H, Seishima M. Adsorptive Depletion of CD14+CD16+Proinflammatory Monocyte Phenotype in Patients With Generalized Pustular Psoriasis: Clinical Efficacy and Effects on Cytokines. Ther Apher Dial 2012; 16:436-44. [DOI: 10.1111/j.1744-9987.2012.01108.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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C Leitner G, Worel N, Vogelsang H. Selective Granulocyte and Monocyte Apheresis as a Non-Pharmacological Option for Patients with Inflammatory Bowel Disease. ACTA ACUST UNITED AC 2012; 39:246-252. [PMID: 22969694 DOI: 10.1159/000341801] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2012] [Accepted: 07/11/2012] [Indexed: 12/18/2022]
Abstract
Ulcerative colitis and Crohn's disease are the two most prevalent inflammatory bowel diseases. In both cases, the medically refractory and steroid-dependent type presents a therapeutic challenge. To help resolve this problem, a mainly Japanese team developed a new therapeutic option. There are two systems, both of which are able to selectively remove the main mediators of the disease, namely the activated pro-inflammatory cytokine-producing granulocytes and monocytes/macrophages, from the patient's blood circulation (GMA = granulocyte monocyte apheresis). One of the two systems is the Adacolumn( (®) ) (Immunoresearch Laboratories, Takasaki, Japan) consisting of the ADA-monitor and a single-use column, which contains approximately 35,000 cellulose acetate beads. The exact mode of action is not yet sufficiently understood, but however, a modulation of the immune system takes place. As a result, less pro-inflammatory cytokines are released. Furthermore, the production of anti-inflammatory interleukin-1 receptor antagonist is increased, and the apoptosis of granulocytes boosted. The decreased LECAM-1-expression on leukocytes impedes the leukotaxis to the inflamed tissue, and CD10-negative immature granulocytes appear in the peripheral blood. Another effect to be mentioned is the removal of the peripheral dendritic cells and the leachate of regulatory T cells (T-regs). The second system is the Cellsorba( (®) ) FX Filter (Asahi Medical, Tokyo, Japan). The range of efficiency, the indication, and the procedure are very similar to the Adacolumn. Solely the additional removal of lymphocytes can possibly limit the implementation since lymphopenia can increase the risk of autoimmune disease. Both systems provide a low-risk therapy with few adverse reactions. ASFA recommendations for GMA in inflammatory bowel disease are 2B due to the fact that not enough randomized double-blind studies are available to proof the efficacy of this treatment.
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Affiliation(s)
- Gerda C Leitner
- University Clinic for Blood Group Serology and Transfusion Medicine, Vienna, Austria
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Sanchez-Garcia J, Serrano-López J, García-Sanchez V, Alvarez-Rivas MA, Jimenez-Moreno R, Pérez-Seoane C, Herrera-Arroyo C, Serrano J, de Dios JF, Torres-Gomez A. Tumor necrosis factor-α-secreting CD16+ antigen presenting cells are effectively removed by granulocytapheresis in ulcerative colitis patients. J Gastroenterol Hepatol 2010; 25:1869-75. [PMID: 21091999 DOI: 10.1111/j.1440-1746.2010.06377.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM In human blood, two main subsets of antigen-presenting-cells (APCs) have been described: plasmocytoid dendritic cells (pDC) and myeloid dendritic cells (mDC) which are further subdivided in CD11c-mDC and CD16-mDC DC. In ulcerative colitis patients (UC) peripheral blood APCs express significant levels of the activation and lack immature-tolerogeneic APCs. Adacolumn selective granulocytapheresis (GCAP) has been associated with clinical efficacy in patients with UC. In the present study we sought the effect of sequential GCAP procedures in peripheral blood APCs in patients with UC and the effect on soluble cytokines. METHODS We used multiparametric flow cytometry to quantify peripheral blood APCs and serum cytokines in 210 samples obtained from seven patients with steroid-dependent or steroid resistant UC undergoing GCAP treatment. Samples were drawn before, after 30 and 60 min of each session. RESULTS Each GCAP session resulted in a dramatic tenfold reduction of peripheral blood CD16-mDC (P < 0.01), pDC decreased twofold (P = 0.05) but CD11c-mDC remained unchanged. This depletion was reached after 30 min and maintained at 60 min. The depletion of CD16-mDC and monocytes was associated with a reduction of serum tumor necrosis factor levels and a raise in interleukin-10 levels, although no statistical difference was reached. CONCLUSION The effect of GCAP in peripheral blood APC consisted mainly on a significant depletion of tumor necrosis factor-α secreting CD16-mDC. This finding could suggest a potential mechanism of GCAP beneficial effect that must be confirmed in larger series.
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Affiliation(s)
- Joaquin Sanchez-Garcia
- Department of Hematology and Laboratory for Cellular Therapy, University Hospital Reina Sofía, Cordoba, Spain.
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Adsorptive depletion of alpha4 integrin(hi)- and CX3CR1hi-expressing proinflammatory monocytes in patients with ulcerative colitis. Dig Dis Sci 2010; 55:1886-95. [PMID: 19908144 DOI: 10.1007/s10620-009-0974-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2009] [Accepted: 08/28/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND Two main functionally distinct monocytes phenotypes are known: the CD14(hi)CD16(-) "classical" and the CD14(+)CD16(+) "proinflammatory" phenotypes. The latter phenotype is elevated in patients with ulcerative colitis (UC) and is suspected to have a major role in the immunopathogenesis of UC. AIM To selectively deplete circulating proinflammatory CD14(+)CD16(+) monocyte phenotype. METHODS Seven corticosteroid-naïve patients with UC (clinical activity index = 8.7 +/- 1.3) and seven healthy subjects were included. In patients with UC, granulocyte/monocyte adsorption (GMA) was done with an Adacolumn that selectively adsorbs leucocytes of the myeloid lineage. Blood from all subjects at baseline and from the patients immediately after the first GMA session was processed. Isolated monocytes were subjected to fluorescence-activated cell sorter analyses. RESULTS The seven UC patients achieved remission (CAI <or=4) after 5-10 GMA sessions. GMA induced a strong fall in the ratio (%) of CD14(+)CD16(+) to CD14(hi)CD16(-) monocytes, from 10.0 +/- 1.4 to 3.0 +/- 0.9. Further, expressions of alpha4 integrin (374.8 +/- 26.1 mean fluorescence intensity, MFI) and CX(3)CR1 (49.5 +/- 4.6 MFI) were significantly high on CD14(+)CD16(+)monocytes as compared with on CD14(hi)CD16(-) monocytes (169.2 +/- 17.2 and 33.2 +/- 3.6 MFI, respectively). Additionally, GMA significantly increased the ratio of the CD14(hi)CD16(-)CCR2(low) "immature" monocytes from 3.74 +/- 0.62 to 8.11 +/- 0.56 MFI. CONCLUSIONS We found high expressions of alpha4 integrin and CX(3)CR1 on monocytes in patients with active UC, known to promote the extravasation of CD14(+)CD16(+) monocytes into the mucosa. GMA effectively depletes CD14(+)CD16(+) monocytes and concomitantly increases CD14(hi)CD16(-)CCR2(low) "immature" monocytes; thus GMA was associated with the emergence of less inflammatory monocyte phenotype in circulation.
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