Monocyte-endothelial cell interaction induces expression of adhesion molecules on human umbilical cord endothelial cells

Objective: The adhesive interaction of monocytes and endothelial cells has been implicated as a regulatory signal in the cell activation that is involved in the pathogenesis of atherosclerosis. We investigated the effect of monocyte-endothelial cell interaction on the expression of adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), in human umbilical cord vein endothelial cells (HUVECs). Methods: ICAM-1 and VCAM-1 protein and mRNA expression were determined by cellular ELISA and Northern blot analysis, respectively, Results: The addition of unstimulated human monocytes, as well as interleukin-1 beta (IL-1 beta: 25 U/ml) and tumor necrosis factor-alpha (TNF: 100 U/ml), to HUVECs rapidly induced the expression of ICAM-1 and VCAM-1 protein and mRNA in HUVECs, whereas the addition of polymorphonuclear leukocytes (PMNs) had no significant effect on their expression. The induction of ICAM-1 and VCAM-1 by the to-culture of HUVECs and monocytes was significantly, bur partially, inhibited by the combination of anti-IL-1 alpha, anti-IL-1 beta and anti-TNF Abs, Actinomycin D and genistein, but not calphostin C, also significantly inhibited the co-culture-induced adhesion molecule expression, Conclusions: These results suggest that the monocyte-endothelial cell interaction induces the expression of ICAM-1 and VCAM-1 in endothelial tells partially through the production of IL-1 and TNF, These findings also suggest that the monocyte-endothelial interaction further augments their interaction through the up-regulation of endothelial adhesion molecules, as a positive feedback mechanism.