NITRIC-OXIDE ATTENUATES ADHESION MOLECULE EXPRESSION IN HUMAN ENDOTHELIAL-CELLS

Leukocyte adhesion to vascular endothelium is a crucial step in the ea rly stages of atherosclerosis, which may be mediated by the interactio n of adhesion molecules expressed on the surfaces of both cell types. in this study, we investigated the effects of nitric oxide OVO) 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 de termined by cellular ELISA and Northern blot analysis, respectively. B oth ICAM-1 and VCAM-1 expression were increased markedly by interleuki n-1 beta(IL-1 beta). This IL-1 beta-mediated induction of ICAM-1 and V CAM-1 expression was significantly inhibited in the presence of a NO d onor 3-morpholino-sydnonimine (SIN-1) in a dose-dependent manner. The inhibitory effect of SIN-1 was abolished in the presence of a NO scave nger haemoglobin, while addition of 8-bromo-cGMP showed no significant effect on IL-1 beta-induced ICAM-1 or VCAM-1 expression. Northern blo t analysis showed that IL-1 beta markedly increased ICAM-1 and VCAM-1 mRNA expression, while SIN-1 decreased the accumulation of these trans cripts induced by IL-1 beta. These results suggest that NO could preve nt the focal adhesion and accumulation of leukocytes through the inhib ition of ICAM-1 and VCAM-1 expression in endothelial cells. (C) 1996 A cademic Press Limited.