Phenotypic Analysis of Inflammatory Infiltrate and Localization of Fibroblast Growth Factor in the Rat with Dimethylnitrosamine-induced Liver Fibrosis

Lee, Sun Kyung; Park, Do Youn

Abstract

BACKGROUND/AIMS: In recent years, knowledge about the role of lymphocytes-macrophages and characterstics of poliferation and activation of fat-storing cells(FSCs) in DMN induced liver fibrosis have greatly increased. However immunologic characteristics of mononuclear cells in this rnodel are not well defined. Furthermore, bFGF has been identified in liver extracts by Western blot, but its cellular lacalixation remains unknown. We have studied lymphocyte subsets and cellular localixation of bFOF in DMN-indueed liver fibmsis vsing an immunohistochemical method.
METHODS
Male Sprague-Dawley rats recieved -1% DMN dissolved in saline at a dose of 10 ul/kg, i.p., 3 conscutive days a week for 3 weeks. The animals were sacrificed on days 7, 14, 21, 28 and 35. We camed out immunostain by indirect three-step immunoperoxidase method for lymphocyte subsets on frozen sections and,ABC rnethod for a-smooth muscle actin as an activation marker of FSCs and bFGF on paraffin sections.
RESULTS
The early stage of DMN treated rats show multiple foci of centrilobular hemcerhagic necrosis infiltrating lymphoeytes and macrophages. CDS(+) T-cells seemed to be the major camponents of the inflammatory infiltrate, and CD4(+) T-cells were also seen around and periportal areas. bFGF was expressed in centrilobular clusters of macrapbages, later in activated FSCs and marginal hepatocytes of regenerating micronoduks. Condusions: CDS(+) T-cell was the major effector cell in DMN-induced liver injury. bFGF was poduced by macrophage and then expressed by PSCs and hepatocyte. Therefore bFGF prornotes produetion of extracellular matrix by FSCs and regeneration of hepatocytes.