Renal tubular epithelial cell self-injury through Fas/Fas ligand interaction promotes renal allograft injury

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
C DuAnthony M Jevnikar

Abstract

Tubular epithelial cells (TECs) coexpress Fas and Fas ligand (FasL), which could influence renal allograft injury. While TECs can resist apoptosis by Fas antibody, TEC apoptosis by contact with adjacent TECs has not been studied. Fas expression increased in TECs with cytokine treatment (IFN-gamma, TNF-alpha) while abundant FasL levels were not altered. Apoptosis (Annexin-V, DNA fragmentation) occurred in cytokine-treated TECs monolayers from C3H-HeJ mice by 24 h, but was absent in similarly treated TECs from Fas-deficient (lpr) or FasL-mutant (gld) mice, suggesting that 'self injury' occurred through Fas/FasL. Membrane labeling of TECs in cocultures confirmed that FasL-bearing TECs induced apoptosis when in contact with Fas-bearing TECs. Culturing TECs with allogeneic C57BL/6 (H-2b) splenocytes resulted in apoptosis and elimination of C3H-HeJ TECs by 48 h, with enhanced survival and reduced apoptosis using lpr or gld TECs. In a renal allograft model, survival of C57BL/6 recipients was greater (p < 0.05) and renal function improved (p < 0.001) using C3H-lpr or C3H-gld (H-2 k) donor kidneys compared with C3H-HeJ kidneys. These data demonstrate for the first time that cytokine-activated TECs can injure TECs through expression of f...Continue Reading

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Citations

Dec 4, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Shuang WangAnthony M Jevnikar
Nov 27, 2008·Transplantation·Chris Y NguanPatrick P W Luke
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May 16, 2008·American Journal of Physiology. Renal Physiology·Kanishka MohibAnthony M Jevnikar
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Nov 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhu-Xu ZhangAnthony M Jevnikar
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Dec 15, 2005·American Journal of Physiology. Renal Physiology·Caigan DuAnthony M Jevnikar

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American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
C DuAnthony M Jevnikar
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C DuAnthony M Jevnikar
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