抄録
The localization of the cholestatic factor (CF), which induces intrahepatic cholestasis, was investigated immunohistochemically. Monoclonal antibody to guinea pig-CF was used in this immunohistochemical study. In liver biopsy specimens obtained from patients with various liver diseases, CF was immunohistochemically detected in seven of nine patients with drug-induced liver injury, three of four patients with acute viral hepatitis, three of five patients with alcoholic liver injury and in the two patients with autoimmune hepatitis. Of these 15 CF-positive patients, fourteen had jaundice during their clinical courses. CF was stained in a diffuse granular pattern in the cytoplasm of the hepatocytes. However, CF was not detected in liver specimens from normal controls and patients with primary biliary cirrhosis and extrahepatic biliary obstruction. Ultrastructural immunohistochemistry revealed that CF was localized on the ribosomes and polysomes as well as on the filamentous structures around the bile canaliculi. Experimentally, CF was immunohistochemically detected in cultured peripheral blood lymphocytes from patients with drug-induced intrahepatic cholestasis. When guinea pig hepatocytes were cultured with the supernatant obtained from human CF-positive lymphocytes culture, CF was stained in a diffuse granular pattern in the cytoplasm of the hepatocytes. However, CF was not present in cultured guinea pig hepatocytes incubated with IL-1, IL-2, IL-6, and TNF as controls. These findings suggest that CF is present in hepatocytes of patients with intrahepatic cholestasis due to various liver diseases and that CF or a CF-like substance is synthesized by hepatocytes in certain intrahepatic cholestatic state and induces intrahepatic cholestasis. It is concluded that CF plays an important role in intrahepatic cholestasis.
