Mast cells distribution in human liver disease and experimental rat liver fibrosis. Indications for mast cell participation in development of liver fibrosis

Abstract

The development of liver fibrosis due to chronic liver diseases is thought to be mediated by inflammatory cells releasing fibrogenic mediators that activate fat-storing cells (Ito-cells). Recently, the involvement of mast cells in fibrogenesis has been suggested. We studied the distribution of these cells in normal human liver and human nonfibrotic and fibrotic liver disease as well as in normal rat liver and acutely and chronically injured rat liver (CCl4 model). Mast cells were identified by histochemical and immunohistochemical methods. The immunoreactivity of liver and comparatively of rat peritoneal mast cells to the serpins alpha1-antitrypsin, alpha1-antichymotrypsin and antithrombin III was also studied. In normal human and rat liver, mast cells were rarely found in portal tracts, and there was no change in cell numbers in nonfibrotic human or acutely injured rat livers. In contrast, cirrhotic human and rat livers contained numerous mast cells in the portal tracts and the fibrous septa. They exhibited strong immunoreactivity to the serpins, as did rat peritoneal mast cells. The results indicate that in the late stages of liver fibrogenesis, mast cells may be involved by displaying protease inhibitory activity in the fibrotic septa.