Roles and Expression Mechanisms of Cellular Adhesion Molecules during the Initiation of Arteriosclerosis

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Expressions of the adhesion molecules in arterial endothelial cells are crucial events during the initiation of arteriosclerosis. Our study showed that endothelial cells expressed endothelial leukocyte adhesion molecule-1 (ELAM-1) occasionally but significantly by oxidized LDL,glycated LDL,H_2O_2, and hypoxic culture mediumin vitro. Also significant factor was immune-complex of oxidized LDL and its auto-antibody. Next we examined temporal relations of induction of ELMA-1, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion mplecule-1 (VCAM-1) in cultured endothelial cells of human thoracic aorta. Activators examined were IL-1alpha (10ng/mL), TNFalpha (10ng/mL), and INFgamma (10ng/mL). Cells were incubated with each of the cytokines for 0.5-48 hours. ELAM-1 was observed by the activations with IL-1 and TNFalpha ; IL-1 gave a sharp rise after an hour incubation and showed the maximum expression at 2 hours, while TNFalpha showed a slow rise after 30 minutes and the maximum at 4 hours. ICAM-1 expression was observed evn in non-stimulated cells and further increased in proportion to duration of the activation. There was no significant difference between the effects of IL-1 and TNFalpha to the ICAM-1 expression. Slight expression of VCAM-1 was observed only by TNFalpha after 2-hours incubation. INFgamma did not cause any change in the expression of ELAM-1, VCAM-1, and ICAM-1. The present data indicate that there appear to be specific signal pathways for each induction of ELAM-1 and VCAM-1, but not ICAM-1. In atherogenesis, therefore, the temporal relations of the molecules may play a role for endothelial cells to discriminate monocytes from other cells such as neutrophils.