| Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient. | |
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MedLine Citation:
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PMID: 15375386 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance. |
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Authors:
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E Sun; Y Gao; J Chen; A I Roberts; X Wang; Z Chen; Y Shi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cell death and differentiation Volume: 11 ISSN: 1350-9047 ISO Abbreviation: Cell Death Differ. Publication Date: 2004 Dec |
Date Detail:
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Created Date: 2004-11-15 Completed Date: 2005-06-17 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 1258-64 Citation Subset: IM; S |
Affiliation:
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Transplantation Department, Zhujiang Hospital, Guangzhou 510282, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Annexin A5 / pharmacology Apoptosis / immunology* Gadolinium / pharmacology Graft Rejection / immunology, prevention & control Graft Survival / immunology* Heart Transplantation / immunology Lymphocyte Transfusion / methods* Lymphocytes / immunology* Male Models, Animal Phagocytosis / immunology* Rats Rats, Sprague-Dawley Rats, Wistar Receptors, Cell Surface / antagonists & inhibitors, metabolism Transplantation Tolerance / immunology* |
| Grant Support | |
ID/Acronym/Agency:
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AI43384/AI/NIAID NIH HHS; AI50222/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Annexin A5; 0/Receptors, Cell Surface; 0/phosphatidylserine receptor; 10138-52-0/gadolinium chloride; 7440-54-2/Gadolinium |
| Investigator | |
Investigator/Affiliation:
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Y Shi / U Med Dentistry NY, Piscataway |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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