| Brain natriuretic peptide induces CD8+ T cell death via a caspase 3 associated pathway - Implications following heart transplantation. | |
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MedLine Citation:
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PMID: 22138041 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Brain natriuretic peptide (BNP) remains elevated after cardiac transplantation despite replacement of the failing ventricle. Serum peaks are also seen during acute rejection episodes independent of intracardiac hemodynamic disturbance. High BNP levels are also reported during bacterial sepsis, burns, stroke and myocardial infarction. Given all of these conditions are linked by immune activation processes, we hypothesised that BNP is an immunoactive agent. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of 40 cardiac transplant recipients. Cells were co-cultured for 72h in the presence or absence of BNP. Cells were then immunophenotyped using flow cytometry. Cell death pathways were determined using caspase 3 quantification and mitochondrial membrane assessment. Supernatants were analysed for cytokine, chemokine and growth factor production using luminex. RESULTS: Co-culture of CD8+ T cells with BNP reduced cell number, and increased intracellular caspase 3. Supernatant analysis revealed that BNP reduced the expression of inflammatory cytokines including TNF-α, IL-1α and IL-6. However it preserved the production of anti-inflammatory and regulatory cytokines such as IL-4, 5 and 13. CONCLUSION: Our findings provide evidence that BNP directly induces CD8+ T cell apoptosis via a caspase 3 associated mechanism from cardiac transplant patients. This may impart significant consequences on immune mediated disease processes, such as allograft rejection. |
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Authors:
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Steven M Shaw; William R Critchley; Christopher M Puchalka; Simon G Williams; Nizar Yonan; James E Fildes |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-30 |
Journal Detail:
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Title: Transplant immunology Volume: - ISSN: 1878-5492 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-12-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9309923 Medline TA: Transpl Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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The Transplant Centre, University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital, Manchester, M23 9LT, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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