Occurrence of cytotoxic autoantibody in rabbits by immunization with heterologous liver arginase: a possible implication in the mechanism of the autoimmune liver diseases.

Rat liver arginase was isolated from extracts of liver in a pure form. Monospecific antisera raised against the arginase reacted with arginase of liver but not with arginase of kidney, spleen, heart, lung, testis and brain. The antisera were, however, reactive with liver arginase of a variety of animals, including human, mouse, sheep, horse and cow as well as rabbit, a homologous animal used for immunization. The rabbit autoantibodies showed direct cytotoxic activity as well as antibody-dependent cell-mediated cytotoxicity to homologous rabbit hepatocytes. Immunocytochemical electron microscopic examination showed that the arginase was localized on the surfaces of rat hepatocytes and on intracellular organelles. These results suggest that liver arginase could be an important antigen of the liver with implications for the pathogenesis of autoimmune liver diseases.