HEPATIC MUCOSAL MAST-CELL HYPERPLASIA IN RATS WITH SECONDARY BILIARY-CIRRHOSIS

Mast cells have been shown to play a role in many chronic inflammatory and fibrotic disorders. However, their possible contribution to the p athological changes that occur in Liver cirrhosis is unknown. To explo re this, we examined whether changes in hepatic mast cell number and m ediator content were associated with fibrotic changes in experimental biliary cirrhosis. Rats were studied 7, 14, or 21 days after bile duct resection (BDR). Hepatic mast cells were identified by histochemical and immunohistochemical stains. Rat mast cell protease II (RMCP-II), a marker of mast cell degranulation, was measured in liver by enzyme-li nked immunosorbent assay. Hepatic collagen deposition was assessed by Sirius Red F3BA staining. In day 21 BDR rats, there was a one- to twof old increase (P < .001) in the number of hepatic mast cells, but this was not observed in day 7 or 14 BDR rats, Mild fibrotic changes were n oted in BDR rat livers as early as 7 days after induction of cholestas is. Significant expansion and organization of fibrous tissue had occur red in day 14 BDR rats which progressed to bridging fibrosis by day 21 . Liver RMCP-II levels were decreased by 50% (P < .05) and mast cell d egranulation was apparent as shown by histamine immunostaining, These results suggest that hepatic mast cell hyperplasia and degranulation o ccur during prolonged cholestasis in the rat. Although these changes d o not correlate with the onset of hepatic fibrosis, they do occur at a time during which there is significant deposition and organization ex tracellular matrix elements. Hepatic mast cells, by releasing profibro genic mediators, may contribute to fibrotic changes in biliary cirrhos is.