Study on the role of mast cells in the development of liver fibrosis during diethylnitrosamine (DEN) -induced hepatocarcinogenesis in rats.

The mast cells (MC) and their roles in the development of liver fibrosis during experimental hepatocarcinogenesis in rats have been studied immunohistochemically and electron microscopically. Pronounced MC hyperplasia occurred after beginning of the treatment of DEN. The vast majority of mast cells in fibrotic livers was present in thickened fibrous septa. Intracellular or pericytial collagen type IV and laminin staining were found in mast cells, collagen types I, III and fibronectin were negative. Mast cells mainly distributed in proximity to basement membrane and the electron microscopical observation revealed a close topographic relationship between mast cells and fibroblasts. The fibroblasts phagocytized the granules released by mast cells and thus were activated, showing enhanced formation of collagenous fibrils. The mast cells may be derived from blood circulation or replicated in situ. Those findings indicated that mast cells take part in the process of fibrosis at least by two ways: (1) It directly synthesizes the basement membrane components; (2) It stimulates the fibroblasts or other types of cells which have the potential functions in fibrogenesis by releasing granule mediators or cytokines acting upon the fibrosis process.