A rat model of acute liver necrosis induced by a monoclonal antibody to liver-specific antigen and complement

Acute massive hepatic injury was induced in rats by a monoclonal antibody against a rat liver-specific membrane antigen, and its histological characteristics were investigated. A single intravenous injection of murine ascites containing a monoclonal antibody produced numerous hemorrhagic foci of degenerated and necrotic liver cells predominantly in zones 1 (the periportal area) and 2 (the area of transition between the periportal zone and the perivenular zone) of the liver lobule within 10 min. Massive hepatocellular necroses were observed 1 hr later, but no inflammatory cell infiltration occurred in and around the necrotic foci. Immunohistological study demonstrated marked deposition of the third component of the complement system in the necrotic area. Serum complement activity was sharply decreased immediately after the injection of the antibody, suggesting that the hepatic necrosis is ascribable to a complement-mediated immune attack on the liver cell membrane induced by the antigen-antibody reaction. The hepatic necrosis in response to monoclonal-antibody injection did not progress to a chronic disease and healed almost completely, changing to scar tissues within 2 wk. Although it is not clear whether this hepatic injury has any clinical relevance, this antibody/complement model may be useful for investigating the cause and therapy of hepatic diseases such as fulminant hepatitis.