Molecular Mechanism of Fas-Mediated Apoptosis in Human Renal Allograft Rejection
| Project/Area Number |
10670179
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | School of Medicine,Toho University |
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Principal Investigator |
AKASAKA Yoshikiyo Second Department of Pathology, School of Medicine, Toho University, Associate Professor, 医学部, 助教授 (60202511)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Takeshi Department of Biology, School of Medicine, Toho University, Professor, 医学部, 教授 (30166714)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Transplanted Kidney / Apoptosis / Fas / Fas ligand / Rejection |
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| Research Abstract |
Immunohistochemically, Fas antigen was highly expressed in the renal tubular epithelium in tissues from patients with rejection. The mean number of Fas-positive tubular epithelium was significantly higher in biopsies with AR than in those with NR (1.56 versus 0.65, P<0.05). In contrast, FasL expression was highly expressed in infiltrating lymphocytes in the interstitium of allografts with cellular rejection. The mean number of FasL-positive infiltrating lymphocytes was significantly higher in biopsies with AR than in those with NR (1.19 versus 0.40, P<0.05) or BS (1.19 versus 0.30, P<0.05), respectively. The mean number of TUNEL signal-positive tubular epithelial cells was highest for the renal allografts with AR : the number being significantly higher than in those with AR plus CR (2.25 versus 1.35, P<0.05) and NR (2.25 versus 1.15, P<0.05), respectively. Thus we speculated that, along with increased FasL expression on infiltrating lymphocytes during AR, Fas expression on epithelial cells may actively trigger their apoptosis by the interaction between Fas and FasL. Studies of two human normal renal-derived cell lines (the proximal tubular epithelial cell line, RPTEC 2601, and the mesangial cell line, NHMC 5155) showed that both constitutively expressed Fas mRNA, but not FasL mRNA. After pretreatment with INF-gamma, Fas-induced apoptosis by anti-Fas monoclonal antibody was observed in the RPTEC 2601 epithelial cell line. However, without INF-g pretreatment, anti-Fas-mediated apoptosis was not induced in the RPTEC 2601 line. Our combined analyses in vivo and in vitro suggest that AR of human allografts might be associated with increased apoptosis in the renal tubular epithelial cells mediated by the Fas/FasL system.
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Report
(3 results)
Research Products
(7 results)
