Liver cell damage caused by monoclonal antibody against an organ-specific membrane antigen in vivo and in vitro.

Monoclonal antibodies have been raised against different antigenic determinants of normal rabbit hepatocytes. One antibody (2D3) recognized a liver-specific 43 kDa protein displayed exclusively on the basolateral portion of the hepatocellular membrane. Purified monoclonal antibodies were injected intravenously into rabbits. Following the injection of antibody 2D3, a dose-dependent increase of liver enzyme activities in sera was observed. Within 8 h, marked morphological alterations of the hepatocytes, including multiple cell necroses, could be demonstrated by light and electron microscopy. When isolated vital rabbit hepatocytes in culture were used as targets, cytotoxic effects of this antibody could also be observed. This indicates that liver cell damage was not due to antibody-dependent cellular cytotoxicity, but was mediated by the antibody itself. Control antibodies did not show these effects. Thus, our results clearly demonstrate that humoral immune reactions against particular liver membrane antigens may play a role in the development of liver diseases, and provide a useful experimental approach for the investigation of their specificity.