FAS ANTIGEN EXPRESSION OF HEPATOCYTES AND ITS MODIFICATION BY IMMUNOSUPPRESSANTS

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 mo dification by immunosuppressive agents such as FK 506 or CsA can theor etically influence allograft survival. Mouse hepatocytes (BALB/c) were isolated and cultured with or without FK 506 or CsA, and Fas-Ag expre ssion was determined by flow cytometry. Fas-Ag expression in the contr ol was 17.2 +/- 2.5% after 24 hr of culture. When FK 506 or CsA was ad ded, Fas-Ag expression with FK 506 at a concentration of 0.01-0.1 mu g /ml was significantly lower than that with CsA (P < 0.05). When the ce lls were incubated with apoptosis-inducing anti-Fas-Ag monoclonal anti body, agarose gel electrophoresis of the control cells yielded a typic al pattern of DNA fragmentations. The cells with FK 506 at 0.01 mu g/m l yielded the least DNA fragmentation. These findings suggested that i n the in vivo setting, the hepatocytes of the allograft would have a l ower chance of being attacked by CTL in the host treated with FK 506.