963-20 MM-LDL Induced Monocyte Binding to HAEC is Mediated by Alpha-4 Chain of VLA-4 but not by VCAM-1

One of the early events in atherosclerosis is adhesion and transmigration of mononuclears into the subendothelium of large arteries. This localized mononuclear recruitment is probably caused by specific leucocyte adhesion molecules expressed by the endothelial cells at these sites. Oxidized LDL has been found to be present in fatty streaks and is suspected to be the cause of progression to a complicated lesion. It has been recently suggested that this selective adhesion of mononuclears is mediated by VCAM-1 expressed by the endothelial cells. Our group has shown that mildly oxidized LDL (MM-LDL) and not highly oxidized LDL (OX-LDL) induces a selective mononuclear binding to human aortic endothelial cells (HAEC) in culture (12). In our effort to further characterise the molecules involved in this adhesion we treated HAEC with MM-LDL for 6 hours and found an increase in monocyte binding by 158 monos/field + 13 (177%) over background binding. An adhesion blocking VCAM-1 antibody (4B9) did not inhibit MM-LDL induced monocyte binding. However a blocking antibody to the alpha 4 chain of VLA-4(L25.3) significantly reduced this binding to 24 monos/field + 7 (26.6%) over the background binding. An antibody to the beta 1 chain of the VLA 4 (PSD2) reduced this binding to 75 monos/field + 5 (93.9%) over the background. The antibody to beta 2 integrin (TS1/18) had no effect on this binding. These data suggest that MM-LDL induced monocyte binding to HAEC is mediated by the alpa 4 chain of the monocyte VLA-4 integrin, the endothelial ligand for which remains to be determined.