Fas-mediated apoptosis of hepatic cells.

While the fas/fas ligand system has been extensively investigated in immuno-competent cells, the place of this system in the physiology and pathophysiology of liver cells remains to be clarified. Although we know that fas is present at the surface of hepatocytes--the main hepatic cells--the role of this membranous protein in physiological conditions is not yet elucidated. However it is the localization of fas on the plasma membrane of hepatocytes which explains why these cells are mainly destroyed by apoptosis--in a picture resembling human fulminant hepatitis--when mice are administered with anti-fas antibodies or fas ligand. It is also established that fas is surexpressed in some human chronic liver diseases, such as those induced by hepatitis B or C virus, a situation which could explain the pathogenesis of some liver lesions occurring during these diseases, such as the apoptosis of hepatocytes in piecemeal necrosis. Finally the fact that caspases, a group of cysteine proteases activated in fas-induced apoptosis, opens the way to inhibition of these enzymes by synthetic peptides and to prevent and treat hepatocyte apoptosis. Demonstration of this possibility has been recently reported in animals presenting fulminant hepatitis induced by anti-fas antibodies.