Tumor Necrosis Factor-o? Stimulates ICAM-1 Expression in Human Vascular Smooth Muscle Cells

Human atherosclerotic plaques contain numerous smooth muscle cells (SMCs) that express intercellular adhesion molecule-1 (ICAM-1). Expression of ICAM-1 in different cells is known to be regulated by tumor necrosis factor-a (TNF-t*), which has recently been found to be present in the intimal thickening of human arteries. Therefore, we studied the effect of TNF-« on ICAM-1 mRNA content and surface expression in cultured human aortic SMCs by using the methods of Northern blotting and immunofluorescence flow cytometry. Under basal conditions of cultivation, ICAM-1 mRNA was not revealed in SMCs. However, treatment of the cells with recombinant human TNF-« induced substantial levels of ICAM-1 mRNA. The content of ICAM-1 on the surface of SMCs also increased in a doseand time-dependent manner after incubation with TNF-t*. Twenty-four hours of treatment with 10 ng/mL TNF-arled to an approximately 10-fold increase in ICAM-1 surface expression in the SMCs. Under the same conditions, pretreatment of SMCs with TNF-e* resulted in a twofold increase of their adhesiveness for monocytes. In the presence of anti-ICAM-1 monoclonal antibody 10F3, monocyte adhesion to TNF-«-pretreated SMCs was significantly inhibited, suggesting that the observed monocyte-SMC interaction involved the ICAM-1 expressed on SMC surfaces as a result of TNF-<x stimulation. These results led us to propose that TNF-« may act a regulator of functional ICAM-1 expression on the SMC surface and thus can increase the possibility of interactions between mononuclear cells and SMCs in atherosclerotic plaques. (Arteriosclerosis and Thrombosis 1993;13:407-414)