NITRIC OXIDE ATTENUATES ADHESION MOLECULE EXPRESSION IN HUMAN ENDOTHELIAL CELLS

Abstract

Leukocyte adhesion to vascular endothelium is a crucial step in the early stages of atherosclerosis, which may be mediated by the interaction of adhesion molecules expressed on the surfaces of both cell types. In this study, we investigated the effects of nitric oxide (NO) on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). ICAM-1 and VCAM-1 protein and mRNA expression were determined by cellular ELISA and Northern blot analysis respectively. Both ICAM-1 and VCAM-1 expression were increased markedly by interleukin-1β (IL-1β). This IL-1β-mediated induction of ICAM-1 and VCAM-1 expression was significantly inhibited in the presence of a NO donor 3-morpholino-sydnonimine (SIN-1) in a dose-dependent manner. The inhibitory effect of SIN-1 was abolished in the presence of a NO scavenger haemoglobin, while addition of 8-bromo-cGMP showed no significant effect on IL-1β-induced ICAM-1 or VCAM-1 expression. Norther blot analysis showed that IL-1β markedly increased ICAM-1 and VCAM-1 mRNA expression, while SIN-1 decreased the accumulation of these transcripts induced by IL-1β. These results suggest that NO could prevent the focal adhesion and accumulation of leukocytes through the inhibition of ICAM-1 and VCAM-1 expression in endothelial cells.