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Abstract

The hepatic stellate cell (HSC), following a fibrogenic stimulus, is transformed from a quiescent to an activated cell. HSC activation results in numerous changes in cellular morphology, cellular metabolism, and in the pattern of gene expression. Many of the changes that are observed in activated HSCs in animal models of hepatic fibrosis are also seen when these cells are activated by culturing on plastic. These changes include morphological changes to a myofibroblast- like cell with the appearance of smooth muscle α-actin, a loss of the retinol stores, an increase in the rough endoplasmic reticulum, and increases in extracellular matrix production, including a dramatic increase in type I collagen. To identify additional genes that are induced or suppressed during HSC activation, we used the differential polymerase chain reaction (PCR) display technique. Using this technique, we isolated a complementary DNA (cDNA) fragment for the intercellular adhesion molecule 1 (ICAM-1). Northern blotting confirmed that the ICAM-1 messenger RNA (mRNA) was expressed in HSCs activated by culture, but not in quiescent, freshly isolated HSCs. The presence of ICAM-1 protein was demonstrated in culture-activated HSCs, but not in quiescent cells by Western blot analysis and immunohistochemical staining. A functional assay was performed, demonstrating that lymphocytes will adhere to activated HSCs and that treatment of these cells with tumor necrosis factor α (TNF-α) increases lymphocyte adherence. Furthermore, ICAM-1 mRNA levels were increased in HSCs activated in rats in vivo after 1 week of bile duct ligation (BDL). Together, these data indicate that ICAM-1 expression is induced following HSC activation and that the HSC may have a direct role in the transmigration of leukocytes from the hepatic sinusoid to sites of tissue damage during the inflammatory response in the liver.