Oxidized LDL-mediated monocyte adhesion to endothelial cells does not involve NFkappaB.

Oxidised LDL (oxLDL) is a key pathogenic mediator of atherogenesis, exhibiting many proatherogenic properties. We have examined the effect of oxLDL on monocyte adhesion in the endothelial cell line, EA.hy 926. This has included the role of endothelial cell adhesion molecule expression (ICAM-1 and VCAM-1), monocyte chemoattractant protein-1 (MCP-1), and the transcription factor NFkappaB in this interaction. In response to oxLDL (10-100 microg/ml), monocyte adhesion to cells increased dose-dependently. Adhesion of oxLDL at 100 microg/ml was equivalent to that seen with TNFalpha (10 ng/ml). Unmodified LDL (nLDL, 100 microg/ml) had no effect. Both oxLDL and nLDL increased MCP-1 mRNA levels. Interestingly, oxLDL had no effect on the expression of ICAM-1 and VCAM-1. In addition NFkappaB was not activated as shown by western blots of IkappaB-alpha degradation and electrophoretic mobility shift assay. In summary these data show that increased monocyte adhesion to EA.hy 926 cells occurs independently of ICAM-1, VCAM-1, and NFkappaB activation and may involve novel adhesive mechanisms. Copyright 2001 Academic Press.