INCREASED EXPRESSION OF MONOCYTE CHEMOTACTIC PROTEIN-1 DURING ACTIVE HEPATIC FIBROGENESIS - CORRELATION WITH MONOCYTE INFILTRATION

Monocyte chemotactic protein (MCP)-1 is a chemoattractant and activato r for circulating monocytes and T lymphocytes. We investigated MCP-1 p rotein and gene expression during chronic liver disease at different s tages, using immunohistochemistry and in situ hybridization, respectiv ely. In normal liver, a modest expression of MCP-1 was confined to few perisinusoidal cells and to bile duct epithelial cells. During chroni c hepatitis, MCP-1 immunostaining and gene expression were evident in the inflammatory infiltrate of the portal tract. In tissue from patien ts with active cirrhosis, MCP-1 expression was clearly up-regulated an d was present in the portal tract, in the epithelial cells of regenera ting bile ducts, and in the active septa surrounding regenerating nodu les. A combination of in situ hybridization for MCP-1 and immunohistoc hemistry showed that activated stellate cells and monocyte/macrophages contribute to MCP-1 expression in vivo together with bile duct epithe lial cells. Comparison of serial sections of liver biopsies from patie nts with various degrees of necroinflammatory activity showed that inf iltration of the portal tracts with monocytes/macrophages is directly correlated with the expression of MCP-1. These data expand previous in vitro studies showing that secretion of MCP-1 may contribute to the f ormation and maintenance of the inflammatory infiltrate observed durin g chronic liver disease.