Inhibition of macrophages with gadolinium chloride alters intercellular adhesion molecule-1 expression in the liver during acute endotoxemia in rats

Cell adhesion molecules are important for localized accumulation of phagocy tes at sites of tissue damage. In the present studies, we analyzed the effe cts of blocking hepatic macrophages on expression of beta(2) integrins and intercellular adhesion molecule-1 (ICAM-1) adhesion molecules on liver cell s during acute endotoxemia, Flow cytometric analysis revealed distinct subp opulations of macrophages from control animals that varied on the basis of their size and density. In contrast, hepatocytes and endothelial cells were relatively homogeneous. Treatment of rats with endotoxin (5 mg/kg, intrave nously) resulted in a time-dependent increase in the percentage of small, d ense macrophages and a progressive loss of larger, less-dense cells. In con trast, no major effects were observed on the physical properties of hepatoc ytes or endothelial cells. ICAM-1 was found to be constitutively expressed on endothelial cells and hepatocytes, as well as on macrophages, Induction of acute endotoxemia resulted in a time-dependent increase in ICAM-1 expres sion on hepatocytes, which was observed within 3 hours and reached a maximu m after 24 hours. An increase in ICAM-1 expression was also observed on end othelial cells and on macrophages at 3 hours, followed by a decrease at 24 to 48 hours. Macrophages and endothelial cells also constitutively expresse d beta(2) integrins. Induction of acute endotoxemia had no effect on beta(2 ) integrin expression by these cells. Pretreatment of rats with gadolinium chloride (GdCl3), a macrophage inhibitor known to block endotoxin-induced l iver injury, abrogated the effects of endotoxin on ICAM-1 expression by hep atocytes and macrophages. In contrast, ICAM-1 expression on endothelial cel ls increased. Interestingly, treatment of rats with GdCl3 alone resulted in a marked increase in expression of ICAM-1 on endothelial cells and hepatoc ytes, and of beta(2) integrins on macrophages and endothelial cells. Taken together, these data suggest that ICAM-1 is involved in mediating macrophag e adherence and accumulation in the liver during endotoxemia. Furthermore, macrophages appear to regulate expression of this cell adhesion molecule on parenchymal cells.