HISTAMINE ENHANCED THE TNF-ALPHA-INDUCED EXPRESSION OF E-SELECTIN ANDICAM-1 ON VASCULAR ENDOTHELIAL-CELLS

Cell adhesion molecules are expressed on endothelial cells by various proinflammatory cytokines. Tumor necrosis factor-alpha (TNF-alpha) ind uces the expression of E-selectin and intercellular adhesion molecule- 1 (ICAM-1) on human umbilical vein endothelial cells (HUVEC). Although histamine is a potent vasoactive mediator, it does not induce the exp ression of E-selectin and ICAM-1. In this report, we show that histami ne concentration-dependently enhances the TNF-alpha-induced expression of E-selectin and ICAM-1 on HUVEC. The histamine-enhanced expression of E-selectin and ICAM-1 was inhibited by the histamine H-1 receptor a ntagonists, mepyramine and diphenhydramine. KW-4679 and ketotifen, ant iallergic drugs with histamine H-1 receptor antagonistic activity, pot ently inhibit the expression of E-selectin and ICAM-1. A histamine H-2 receptor antagonist, ranitidine, did not affect the histamine-induced expression of cell adhesion molecules. These data indicate that hista mine induces the expression of E-selectin and ICAM-1 synergistically w ith TNF-alpha through histamine H-1 receptors. (C) 1996 Academic Press , Inc.