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 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.
Yokoyama
I
I
Department of Surgery II and Equipment Center for Research and Education, Nagoya University, School of Medicine, Japan.
Hayakawa
A
A
Hayashi
S
S
Kobayashi
T
T
Negita
M
M
Takagi
H
H
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D053938:DNA Fragmentation; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D019014:fas Receptor / Q000032:analysis* / Q000276:immunology
D007166:Immunosuppressive Agents; D019014:fas Receptor; D016572:Cyclosporine; D016559:Tacrolimus