Fas antigen expression of hepatocytes and its modification by immunosuppressants

Digestive Diseases and Sciences
I YokoyamaH Takagi

Abstract

Active cell death induced by ligation of the Fas antigen (Fas-Ag) with its antibody, Fas ligand (Fas-L), has been known to play a major role in cell killing via apoptosis by cytotoxic T lymphocytes (CTL). Thus, in liver transplantation, Fas-Ag expression of hepatocytes and its modification by immunosuppressive agents such as FK 506 or CsA can theoretically influence allograft survival. Mouse hepatocytes (BALB/c) were isolated and cultured with or without FK 506 or CsA, and Fas-Ag expression was determined by flow cytometry. Fas-Ag expression in the control was 17.2 +/- 2.5% after 24 hr of culture. When FK 506 or CsA was added, Fas-Ag expression with FK 506 at a concentration of 0.01-0.1 microg/ml was significantly lower than that with CsA (P < 0.05). When the cells were incubated with apoptosis-inducing anti-Fas-Ag monoclonal antibody, agarose gel electrophoresis of the control cells yielded a typical pattern of DNA fragmentations. The cells with FK 506 at 0.01 microg/ml yielded the least DNA fragmentation. These findings suggested that in the in vivo setting, the hepatocytes of the allograft would have a lower chance of being attacked by CTL in the host treated with FK 506.

Citations

Dec 22, 1999·Journal of Viral Hepatitis·N Hayashi, E Mita
Jul 4, 2002·The American Journal of Gastroenterology·M RiveroF Pons-Romero
Sep 12, 2006·Digestive Diseases and Sciences·Yago Gonzalez-LamaJose Mate
Aug 17, 2001·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·R SindhiJ F Dunne
Nov 19, 2004·Biochemical Pharmacology·M J Gómez-LechónJ Mir

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