Fas engagement accelerates liver regeneration after partial hepatectomy

Fas (CD95) is a receptor involved in induction of apoptotic cell death of F as-bearing cells, including hepatocytes(1,2) and T cells(3). Injection of F as-specific antibodies into mice leads to fulminant hepatic failure and dea th(1). Fas also transduces growth-promoting signals in proliferating T cell s(4,5), fibroblasts(6) and some tumor cells'. Here we show that partial hep atectomy, which triggers the immediate onset of liver regeneration(8), prot ected mice against the lethal effects of Fas-specific antibodies and preven ted hepatocyte apoptosis in response to Fas engagement in vivo. Furthermore , Fas engagement accelerated liver regeneration after partial hepatectomy. Liver regeneration kinetics were delayed in mutant mice with decreased cell surface Fas expression (lpr mice(9)), in contrast, regeneration was not de layed in lpr-cg mutant mice, which have a Fas mutation that prevents Fas-in duced death(10) but not Fas-dependent proliferative stimulation. Our result s indicate that Fas engagement on cells in regenerating or healing tissues may promote cell growth.