Renal Ischemia-reperfusion Injury and Adenosine 2a Receptor-mediated Tissue Protection: the Role of Cd4+ T Cells and Ifn-gamma.
From: Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Mar 2006
- ISSN: 0022-1767
- Volume: 176
- Issue: 5
- Pages: 3108-14
- Medium: Print
- Language: English
- Citation (JAMA): Day Yuan-Ji, Huang Liping, Ye Hong, et al. Renal Ischemia-reperfusion Injury and Adenosine 2a Receptor-mediated Tissue Protection: the Role of Cd4+ T Cells and Ifn-gamma.. J. Immunol. Mar 2006;176:3108-14
Abstract
A(2A) adenosine receptor (A(2A)R)-expressing bone marrow (BM)-derived cells contribute to the renal protective effect of A(2A) agonists in renal ischemia-reperfusion injury (IRI). We performed IRI in mice lacking T and B cells to determine whether A(2A)R expressed in CD4+ cells mediate protection from IRI. Rag-1 knockout (KO) mice were protected in comparison to wild-type (WT) mice when subjected to IRI. ATL146e, a selective A(2A) agonist, did not confer additional protection. IFN-gamma is an important early signal in IRI and is thought to contribute to reperfusion injury. Because IFN-gamma is produced by kidney cells and T cells we performed IRI in BM chimeras in which the BM of WT mice was reconstituted with BM from IFN-gamma KO mice (IFN-gamma KO — >WT chimera). We observed marked reduction in IRI in comparison to WT — >WT chimeras providing additional indirect support for the role of T cells. To confirm the role of CD4+ A(2A)R in mediating protection from IRI, Rag-1 KO mice were subjected to ischemia-reperfusion. The protection observed in Rag-1 KO mice was reversed in Rag-1 KO mice that were adoptively transferred WT CD4+ cells (WT CD4+ — >Rag-1 KO) or A(2A) KO CD4+ cells (A(2A) KO CD4+ — >Rag-1 KO). ATL146e reduced injury in WT CD4+ — >Rag-1 KO mice but not in A(2A) KO CD4+ — >Rag-1 KO mice. Rag-1 KO mice reconstituted with CD4+ cells derived from IFN-gamma KO mice (IFN-gamma CD4+ — >Rag-1 KO) were protected from IRI; ATL146e conferred no additional protection. These studies demonstrate that CD4+ IFN-gamma contributes to IRI and that A(2A) agonists mediate protection from IRI through action on CD4+ cells.
Mesh Headings (Keywords): Animals, B-Lymphocytes, Bone Marrow, CD4-Positive T-Lymphocytes, Cells, Cultured, Cyclohexanecarboxylic Acids, Cytoprotection, Homeodomain Proteins, Immunity, Natural, Interferon Type II, Kidney, Lymphopenia, Mice, Mice, Inbred C57BL, Mice, Knockout, Purines, Receptors, Adenosine A2, Reperfusion Injury, T-Lymphocytes
Check for Full Text / PubMed Unique Identifier (PMID): 16493070
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