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Fernandez Sanchez J, Maknojia AA, King KY. Blood and guts: how the intestinal microbiome shapes hematopoiesis and treatment of hematologic disease. Blood 2024; 143:1689-1701. [PMID: 38364184 PMCID: PMC11103099 DOI: 10.1182/blood.2023021174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/18/2024] [Accepted: 02/05/2024] [Indexed: 02/18/2024] Open
Abstract
ABSTRACT Over the past 10 years, there has been a marked increase in recognition of the interplay between the intestinal microbiome and the hematopoietic system. Despite their apparent distance in the body, a large literature now supports the relevance of the normal intestinal microbiota to steady-state blood production, affecting both hematopoietic stem and progenitor cells as well as differentiated immune cells. Microbial metabolites enter the circulation where they can trigger cytokine signaling that influences hematopoiesis. Furthermore, the state of the microbiome is now recognized to affect outcomes from hematopoietic stem cell transplant, immunotherapy, and cellular therapies for hematologic malignancies. Here we review the mechanisms by which microbiotas influence hematopoiesis in development and adulthood as well as the avenues by which microbiotas are thought to impact stem cell transplant engraftment, graft-versus-host disease, and efficacy of cell and immunotherapies. We highlight areas of future research that may lead to reduced adverse effects of antibiotic use and improved outcomes for patients with hematologic conditions.
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Affiliation(s)
- Josaura Fernandez Sanchez
- Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX
| | - Arushana A. Maknojia
- Program in Immunology and Microbiology, Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, TX
| | - Katherine Y. King
- Program in Immunology and Microbiology, Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, TX
- Division of Infectious Diseases, Department of Pediatrics, and Center for Cell and Gene Therapy, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX
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Parasar P, Bernard M, Ahn SH, Kshirsagar SK, Nguyen SL, Grzesiak GR, Vettathu M, Martin D, Petroff MG. Isolation and characterization of uterine leukocytes collected using a uterine swab technique. Am J Reprod Immunol 2022; 88:e13614. [PMID: 35997140 PMCID: PMC9787928 DOI: 10.1111/aji.13614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Revised: 07/07/2022] [Accepted: 08/15/2022] [Indexed: 12/31/2022] Open
Abstract
PROBLEM Leukocytes from the maternal-fetal interface are a valuable tool to study local changes in immune function during pregnancy; however, sampling can be challenging due to inadequate tissue availability and the invasive nature of placental bed biopsy. Here, we aim to purify and characterize leukocytes from paired peripheral and uterine blood samples to assess whether a less invasive method of uterine blood collection could yield a population of enriched uterine leukocytes suitable for ex vivo and in vitro analyses. METHOD OF STUDY Human peripheral blood mononuclear cells (PBMC) and uterine blood mononuclear cells (UBMC) expressed from surgical gauze post C-section were isolated, and immunophenotypic information was acquired by multi-parameter flow cytometry. PBMC and UBMC were stained for markers used to define T and B lymphocytes, macrophages, regulatory T (TReg ) cells, and natural killer (NK) cells. Prime flow was performed to check expression and analysis of CD16- CD56++ and CD16- CD56++ NK transcripts in PBMC and UBMC samples. RESULTS Immunophenotyping revealed that over 95% of both live PBMC and UBMC consisted of CD45+ leukocytes. Higher percentages of CD16- CD56++ , characterized as uterine NK (uNK) cells, were observed in UBMC samples as compared to PBMC samples (18.41% of CD45+ CD3- vs. 2.73%, respectively), suggesting that CD16- CD56++ cells were enriched in these samples. In UBMC, 49.64% of CD3-negative cells were of peripheral NK phenotype (CD16+ CD56++ ), suggesting infiltration of maternal peripheral NK (pNK) cell in the uterine interface. CONCLUSION Intrauterine leukocytes, especially CD16- CD56++ NK cells, can be collected in sufficient numbers with increased purity by sampling the uterine cavity postdelivery with surgical gauze. Our results suggest that this non-invasive protocol is a useful sampling technique for isolating CD16- CD56++ cells, however, due to peripheral blood contamination, the NK cell yield could be lower compared to actual decidual or endometrial samples post-partum which is more invasive.
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Affiliation(s)
- Parveen Parasar
- Department of Pathobiology & Diagnostic InvestigationChildren's Hospital BostonEast LansingMichiganUSA
| | - Matthew Bernard
- Department of Pharmacology & ToxicologyMichigan State UniversityEast LansingMichiganUSA
| | - Soo Hyun Ahn
- Department of Pathobiology & Diagnostic InvestigationChildren's Hospital BostonEast LansingMichiganUSA
| | - Sarika K. Kshirsagar
- Department of Pathobiology & Diagnostic InvestigationChildren's Hospital BostonEast LansingMichiganUSA
| | - Sean L. Nguyen
- Cell and Molecular Biology ProgramMichigan State UniversityEast LansingMichiganUSA,Institute for Integrative ToxicologyMichigan State UniversityEast LansingMichiganUSA
| | - Geoffrey R. Grzesiak
- Department of Pathobiology & Diagnostic InvestigationChildren's Hospital BostonEast LansingMichiganUSA
| | - Mathew Vettathu
- Department of Obstetrics & GynecologySparrow HospitalEast LansingMichiganUSA
| | - Denny Martin
- Department of Obstetrics & GynecologySparrow HospitalEast LansingMichiganUSA
| | - Margaret G. Petroff
- Department of Pathobiology & Diagnostic InvestigationChildren's Hospital BostonEast LansingMichiganUSA,Cell and Molecular Biology ProgramMichigan State UniversityEast LansingMichiganUSA,Microbiology & Molecular GeneticsMichigan State UniversityEast LansingMichiganUSA
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Abstract
The immune (innate and adaptive) system has evolved to protect the host from any danger present in the surrounding outer environment (microbes and associated MAMPs or PAMPs, xenobiotics, and allergens) and dangers originated within the host called danger or damage-associated molecular patterns (DAMPs) and recognizing and clearing the cells dying due to apoptosis. It also helps to lower the tissue damage during trauma and initiates the healing process. The pattern recognition receptors (PRRs) play a crucial role in recognizing different PAMPs or MAMPs and DAMPs to initiate the pro-inflammatory immune response to clear them. Toll-like receptors (TLRs) are first recognized PRRs and their discovery proved milestone in the field of immunology as it filled the gap between the first recognition of the pathogen by the immune system and the initiation of the appropriate immune response required to clear the infection by innate immune cells (macrophages, neutrophils, dendritic cells or DCs, and mast cells). However, in addition to their expression by innate immune cells and controlling their function, TLRs are also expressed by adaptive immune cells. We have identified 10 TLRs (TLR1-TLR10) in humans and 12 TLRs (TLR1-TLR13) in laboratory mice till date as TLR10 in mice is present only as a defective pseudogene. The present chapter starts with the introduction of innate immunity, timing of TLR evolution, and the evolution of adaptive immune system and its receptors (T cell receptors or TCRs and B cell receptors or BCRs). The next section describes the role of TLRs in the innate immune function and signaling involved in the generation of inflammation. The subsequent sections describe the expression and function of different TLRs in murine and human adaptive immune cells (B cells and different types of T cells, including CD4+T cells, CD8+T cells, CD4+CD25+Tregs, and CD8+CD25+Tregs, etc.). The modulation of TLRs expressed on T and B cells has a great potential to develop different vaccine candidates, adjuvants, immunotherapies to target various microbial infections, including current COVID-19 pandemic, cancers, and autoimmune and autoinflammatory diseases.
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Affiliation(s)
- Vijay Kumar
- Children's Health Queensland Clinical Unit, School of Clinical Medicine, Faculty of Medicine, Mater Research, University of Queensland, Brisbane, QLD, Australia.
- School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
- Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center (UTHSC), Memphis, TN, USA.
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Li Y, Chen Q, Ji W, Fan Y, Huang L, Chu C, Zhou W. TLR2 deficiency promotes IgE and inhibits IgG1 class-switching following ovalbumin sensitization. Ital J Pediatr 2021; 47:162. [PMID: 34315511 PMCID: PMC8314519 DOI: 10.1186/s13052-021-01088-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 05/03/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND To explore the roles of Toll-like receptor (TLR)2 in Th2 cytokine production and immunoglobulin (Ig) class switching following ovalbumin (OVA) sensitization. METHODS TLR2-/- and wild-type C57BL/6 mice were sensitized by intraperitoneal injection with OVA. Lung pathology was assessed by hematoxylin and eosin staining. Abundance of interleukin (IL)4, IL5, IL13, and IL21 transcripts in the lungs was quantified by RT-PCR. OVA-specific IgG1, IgG2a, IgG2b, IgE and IgM were quantified by enzyme-linked immunosorbent assay. Phosphorylated signal transducer and activator of transcription (STAT)3 in lung tissue was detected by immunohistochemistry staining and nuclear factor (NF) κB activation was measured by immunofluorescence staining. STAT3 activation was inhibited using cryptotanshinone (CPT) treatment. Germline transcripts (Iμ-Cμ, Iγ-Cγ, Iα-Cα or Iε-Cε), post-recombination transcripts (Iμ-Cγ, Iμ-Cα or Iμ- Cε) and mature transcripts (VHDJH-Cγ, VHDJH-Cα or VHDJH-Cε) were analyzed from splenic B cells of OVA-sensitized wild-type mice (with or without CPT treatment) and TLR2-/- mice (with or without IL21 treatment). RESULTS The lungs of TLR2-/- mice showed a lesser degree of inflammation than wild-type mice after OVA sensitization. Following OVA sensitization, levels of IL4, IL13, and IL21, but not IL5, were significantly lower in TLR2-/- compared with wild-type mice. Moreover, OVA-specific IgG1 and IgE titers were markedly lower and higher, respectively, in TLR2-/- mice. TLR2 deficiency inhibited STAT3 activation but not NF-κB p65 activation. CPT treatment reduced IgG1 titers via inhibition of Stat3 phosphorylation. Both TLR2 knockout and CPT treatment reduced the frequencies of Iγ1-Cγ1, Iγ3-Cγ3 and Iα-Cα transcripts, but IL21 treatment compensated for the effects of TLR2 deficiency. CONCLUSION These results suggest a role of TLR2 in restricting OVA-sensitized lung inflammation via promotion of IgG1 and inhibition of IgE class switching regulated by IL21 and STAT3.
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Affiliation(s)
- Yuqin Li
- Children’s Hospital of Soochow University, Suzhou, 215003 People’s Republic of China
| | - Qiu Chen
- School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123 China
| | - Wei Ji
- Children’s Hospital of Soochow University, Suzhou, 215003 People’s Republic of China
| | - Yujie Fan
- Children’s Hospital of Soochow University, Suzhou, 215003 People’s Republic of China
| | - Li Huang
- Children’s Hospital of Soochow University, Suzhou, 215003 People’s Republic of China
| | - Chu Chu
- Children’s Hospital of Soochow University, Suzhou, 215003 People’s Republic of China
| | - Weifang Zhou
- Children’s Hospital of Soochow University, Suzhou, 215003 People’s Republic of China
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Li Q, Wang J, Islam H, Kirschning C, Lu H, Hoffmann D, Dittmer U, Lu M. Hepatitis B virus particles activate B cells through the TLR2-MyD88-mTOR axis. Cell Death Dis 2021; 12:34. [PMID: 33414473 PMCID: PMC7791069 DOI: 10.1038/s41419-020-03284-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/18/2020] [Accepted: 11/25/2020] [Indexed: 02/08/2023]
Abstract
Host immune control plays a pivotal role in resolving primary hepatitis-B-virus (HBV) infections. The complex interaction between HBV and host immune cells, however, remains unclear. In this study, the transcriptional profiling of specimens from animals infected with woodchuck hepatitis virus (WHV) indicated TLR2 mRNA accumulation as most strongly impacted during WHV infection resolution as compared to other mRNAs. Analysis of blood transcriptional modules demonstrated that monocytes and B-cells were the predominantly activated cell types in animals that showed resolution of infection, which was similar to the response of TLR2-stimulated PBMCs. Further investigation of TLR2-stimulated B-cells pointed at interactions between activated TLR signaling, Akt-mTOR, and glucose metabolic pathways. Moreover, analysis of B-cells from Tlr2-/-, Trif-/-, Myd88-/-, and Trif/Myd88-/- mice challenged with HBV particles indicated B-cell function and glucose metabolism alterations is TLR2-MyD88-mTOR axis dependent. Overall, our study implicates B-cell TLR2 activation in HBV infection resolution.
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Affiliation(s)
- Qian Li
- Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.,Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China
| | - Jun Wang
- Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.,Center of Clinical Laboratory, The Fifth People's Hospital of Wuxi, Jiangnan University, Wuxi, Jiangsu, China.,Bioinformatics and Computational Biophysics, University of Duisburg-Essen, Essen, Germany
| | - Heba Islam
- Institute of Medical Microbiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
| | - Carsten Kirschning
- Institute of Medical Microbiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
| | - Hongzhou Lu
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China
| | - Daniel Hoffmann
- Bioinformatics and Computational Biophysics, University of Duisburg-Essen, Essen, Germany
| | - Ulf Dittmer
- Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
| | - Mengji Lu
- Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
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Positive selection of type II collagen-reactive CD80 high marginal zone B cells in DBA/1 mice. Clin Immunol 2017; 178:64-73. [DOI: 10.1016/j.clim.2017.01.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Revised: 01/24/2017] [Accepted: 01/31/2017] [Indexed: 12/23/2022]
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Samitas K, Malmhäll C, Rådinger M, Ramos-Ramirez P, Lu Y, Deák T, Semitekolou M, Gaga M, Sjöstrand M, Lötvall J, Bossios A. Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor. PLoS One 2016; 11:e0161161. [PMID: 27513955 PMCID: PMC4981371 DOI: 10.1371/journal.pone.0161161] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Accepted: 08/01/2016] [Indexed: 11/18/2022] Open
Abstract
Background B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive. Methods A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors (CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of asthmatic patients and healthy controls. Results Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40, CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics. Conclusion Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation.
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Affiliation(s)
- Konstantinos Samitas
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Cellular Immunology Laboratory, Division of Cell Biology, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
- 7th Respiratory Medicine Dept. and Asthma Center, Athens Chest Hospital “Sotiria”, Athens, Greece
| | - Carina Malmhäll
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Madeleine Rådinger
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Patricia Ramos-Ramirez
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - You Lu
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Tünde Deák
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Maria Semitekolou
- Cellular Immunology Laboratory, Division of Cell Biology, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
| | - Mina Gaga
- 7th Respiratory Medicine Dept. and Asthma Center, Athens Chest Hospital “Sotiria”, Athens, Greece
| | - Margareta Sjöstrand
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Jan Lötvall
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Apostolos Bossios
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- * E-mail:
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Wang L, Wang K, Zou ZQ. Crosstalk between innate and adaptive immunity in hepatitis B virus infection. World J Hepatol 2015; 7:2980-2991. [PMID: 26730277 PMCID: PMC4691701 DOI: 10.4254/wjh.v7.i30.2980] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 11/11/2015] [Accepted: 12/11/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a major public health problem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is responsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection.
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Moro AM, Brucker N, Charão MF, Sauer E, Freitas F, Durgante J, Bubols G, Campanharo S, Linden R, Souza AP, Bonorino C, Moresco R, Pilger D, Gioda A, Farsky S, Duschl A, Garcia SC. Early hematological and immunological alterations in gasoline station attendants exposed to benzene. ENVIRONMENTAL RESEARCH 2015; 137:349-356. [PMID: 25601738 DOI: 10.1016/j.envres.2014.11.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Revised: 11/01/2014] [Accepted: 11/04/2014] [Indexed: 06/04/2023]
Abstract
INTRODUCTION Elucidation of effective biomarkers may provide tools for the early detection of biological alterations caused by benzene exposure and may contribute to the reduction of occupational diseases. This study aimed to assess early alterations on hematological and immunological systems of workers exposed to benzene. METHODS Sixty gasoline station attendants (GSA group) and 28 control subjects were evaluated. Environmental and biological monitoring of benzene exposure was performed in blood and urine. The potential effect biomarkers evaluated were δ-aminolevulinate dehydratase (ALA-D) activity, CD80 and CD86 expression in lymphocytes and monocytes, and serum interleukin-8 (IL-8). The influence of confounding factors and toluene co-exposure were considered. RESULTS Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, reduced ALA-D activity, decreased CD80 and CD86 expression in monocytes and increased IL-8 levels were found in the GSA group compared to the control subjects. Furthermore, according to multiple linear regression analysis, benzene exposure was associated to a decrease in CD80 and CD86 expression in monocytes. CONCLUSIONS These findings suggest, for the first time, a potential effect of benzene exposure on ALA-D activity, CD80 and CD86 expression, IL-8 levels, which could be suggested as potential markers for the early detection of benzene-induced alterations.
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Affiliation(s)
- Angela M Moro
- Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Post-Graduate Programme in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Natália Brucker
- Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Post-Graduate Programme in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Mariele F Charão
- Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Post-Graduate Programme in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Elisa Sauer
- Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Post-Graduate Programme in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Fernando Freitas
- Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Juliano Durgante
- Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Guilherme Bubols
- Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Sarah Campanharo
- Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Rafael Linden
- Health Sciences Institute, Feevale University, Novo Hamburgo, RS, Brazil
| | - Ana P Souza
- Laboratory of Cellular and Molecular Immunology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Cristina Bonorino
- Laboratory of Cellular and Molecular Immunology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Rafael Moresco
- Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Diogo Pilger
- Post-Graduate Programme in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Adriana Gioda
- Department of Chemistry of Pontifical Catholic University Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Sandra Farsky
- Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Albert Duschl
- Department of Molecular Biology, University of Salzburg, Salzburg, Austria
| | - Solange C Garcia
- Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Post-Graduate Programme in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
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