REGULATION OF ENDOTHELIAL ADHESION MOLECULES BY LIGANDS BINDING TO THE SCAVENGER RECEPTOR

Monocyte adherence to the endothelium, their penetration to the subend othelial space and excessive lipid accumulation (foam cell formation) are the initial events in atherogenesis. Scavenger receptors have been reported to play an important role in foam cell formation, since modi fied low density lipoproteins can be taken up via scavenger receptors in a non-down-regulated fashion. In this study we demonstrate that sti mulation of scavenger receptors in endothelial cells induces the expre ssion of endothelial adhesion molecules. Polyinosinic acid (poly I), a known scavenger receptor ligand, significantly induced the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on human umbilical vein endothelia l cells when compared with polycytidylic acid (poly C), a structurally related compound to poly I, which does not bind to the scavenger rece ptor. The effect of scavenger receptor ligands on the endothelial cell line EA hy. 926 was also tested. Poly I up-regulated ICAM-1 expressio n also on EA hy. 926 cells, while it had no effect on IL-1beta or tumo ur necrosis factor-alpha (TNF-alpha) production on the same cell line. Poly I-induced ICAM-1 expression on EA hy. 926 cells could be inhibit ed by H7, a protein kinase C inhibitor, while HA 1004, a preferential protein kinase A inhibitor, had no effect on ICAM-1 expression. The ro le of protein kinase C in scavenger receptor-mediated adhesion molecul e up-regulation was confirmed by the ability of poly I to directly act ivate protein kinase C, when measured with H-3-phorbol dibutyrate bind ing to EA hy. 926 cells, while poly C again was ineffective.