Release of bile canalicular membrane antigen into blood in experimental extrahepatic cholestasis of the rat

The level of a bile canalicular membrane antigen in serum during extrahepatic cholestasis was serially analyzed using HAM.4, a monoclonal antibody against a bile canalicular membrane glycoprotein of normal rat hepatocytes. After bile duct ligation, the level of HAM.4 antigen in serum promptly increased within 1 hr, reached a maximum at 3 hr, and declined somewhat until 48 hr, where it plateaued. Elevated levels of HAM.4 antigen in serum preceded those of well-known biliary marker enzymes activities. Immunohistochemical studies showed that the expression of HAM.4 antigen in hepatocytes and bile duct cells was not altered appreciably after bile duct ligation even when HAM.4 antigen in serum reached a maximal level. The serum and hepatic HAM.4 antigen had a molecular weight of 110 kDa. These results suggest that HAM.4 antigen may be regarded as a potential marker of the early stage of cholestasis, with release occurring before apparent histological changes.