Histamine augments VCAM-1 expression on IL-4- and TNF-alpha-stimulated human umbilical vein endothelial cells.

Abstract

Interaction between vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells and CD49d molecules on eosinophils is thought to mediate the selective infiltration of eosinophils into inflamed tissues in allergic disease. IL-4 and TNF-alpha are associated with allergic conditions, and they have been shown to selectively augment VCAM-1 expression on endothelial cells, suggesting that they may be responsible for VCAM-1 expression in allergic disease. We used immunocytochemical staining analysis to examine the effect of chemical mediators, including histamine, leukotrienes and platelet-activating factor (PAF), on VCAM-1 expression in IL-4- and TNF-alpha-stimulated endothelial cells. Histamine, significantly augmented (p < 0.05 to p < 0.01) VCAM-1 expression in both IL-4- and TNF-alpha-stimulated endothelial cells. IL-4 and TNF-alpha were found to have a synergistic effect on endothelial cell VCAM-1 expression, when compared with the effect of stimulation with each of these cytokines separately, and the addition of histamine further increased VCAM-1 expression. This enhancing effect of histamine was inhibited by the presence of mepyramine and thioperamide but not by cimetidine. Another chemical mediator, PAF, failed to induce any increase in VCAM-1 expression, however, leukotrienes augmented it slightly in a narrow range of concentrations. The histamine-induced augmentation of VCAM-1 expression was reflected functionally by many more eosinophils attaching to endothelial cells than to cells stimulated with both cytokines. This attachment of eosinophils was inhibited by the presence of antibody to VCAM-1 and CD49d. Addition of histamine 10 h after stimulation with both cytokines still induced an increase in VCAM-1 expression. In addition, an inhibitor of RNA polymerase, alpha-amanitin, dose-dependently decreased this histamine-induced augmentation of VCAM-1 expression. These findings strongly suggest that histamine upregulates VCAM-1 expression at the transcriptional level through newly generated of mRNA in endothelial cells stimulated with IL-4 and TNF-alpha.