Eosinophilic infiltration of the portal tracts is frequently seen in the early stages of primary biliary cirrhosis. The mechanism of this infiltration is unclear. Nonetheless it is likely that chemokines and/or their cognante receptors are involved. Multiple C-C chemokines including monocyte chemoattractant protein (MCP)-2, MCP-3, MCP-4, RANTES and eotaxin are known to target eosinophils. Eotaxin, in particular, is unique among C-C chemokines because eotaxin activity is limited to eosinophils. In fact eotaxin has been proposed to be both an eosinophil activator and a chemoattractor. In this study, we examined the expression of eotaxin and RANTES in various liver diseases to clarify the mechanism of eosinophilic infiltration in primary biliary cirrhosis. Our data suggest that RANTES is commonly expressed on biliary epithelial cells even in normal livers. In contrast eotaxin was not uniformly expressed on biliary epithelial cells and hepatocytes. Interestingly, however, there were a significant number of eotaxin positive mononuclear cells infiltrated in the portal tract and, especially, near damaged bile ducts in patients with primary biliary cirrhosis. Moreover, using double immunostaining, most eotaxin positive cells near damaged ducts co-expressed CD68, a marker of macrophages. Our data suggest that generic biliary expression of RANTES may play a role in focusing and or homing of precursor macrophages and eosinophils near biliary epithelial cells. In addition, in response to inflammation and/or infection of biliary epithelial cells, these inflammatory cells may become activated and thence express eotaxin; this leads to recruitment of eosinophils around the damaged bile ducts. Clarification of the initial events responsible for eotaxin expression around damaged bile ducts may be a clue to the pathogenesis of primary biliary cirrhosis.
- Primary biliary cirrhosis
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