Mast cells and the activation of interstitial cells in rat liver fibrosis induced by ligation of common bile ducts

Mast cells, distributed in almost all tissues and organs, play significant roles in inflammation. They increase in number in the various fibrotic lesi ons. Mediators secreted from mast cells are known to promote the proliferat ion of fibroblasts and accentuate fibroblastic collagen synthesis. In the l iver, a few mast cells are mainly localized in the portal areas and increas e in number in cirrhosis, although their relevance to fibrogenesis remains obscure. We investigated the interaction between the mast cells and interst itial cells in rat liver fibrosis induced by common bile duct ligation (BDL ) and found a degranulation of the mast calls in the livers at 6, 12 and 18 hours after BDL. After 24 hours portal interstitial cells became positive for alpha-smooth muscle actin (ASMA). Mast cells were in close contact with the ASMA-positive interstitial cells, on the 7th day after BDL, with a pro gression of fibrosis, considerable numbers of ASMA-positive cells appeared in the periportal area, They appeared to be derived from perilobular Ito ce lls. Moreover, immunohistochemical study showed that the granules of mast c ells were positive for transforming growth factor-beta (TGF-beta). These fi ndings suggest that the mast cells in portal areas may contribute to the my ofibroblastic transformation of periductular interstitial cells in the earl y stage of experimental biliary liver fibrosis and also to the activation o f perilobular Ito cells in the fibrotic stage.