Fc-dependent binding of monocytes to areas with endothelial injury in the rabbit aorta

IgG accumulates in injured endothelial cells and nonendothelialized intima. In experimental atherosclerosis, such areas contain large amounts of monocytes. The hypothesis was raised that IgG in areas with endothelial injury (defective endothelium) stimulates monocyte binding via the Fc receptor. This hypothesis was tested in an in vitro system using segments of rabbit thoracic aorta in perfusion chambers. The chambers were initially perfused with autologous serum, permitting the binding of IgG to defective endothelium. Then, autologous mononuclear cells were injected. Monocytes adhered preferentially to defective endothelium, as indicated by a 10-fold increase when compared to intact endothelium. Some lymphocytes also adhered to defective endothelium, but there was a 4-fold increase in the monocyte/lymphocyte ratio on defective endothelium, as compared to the injected cells. The number of monocytes on defective endothelium was reduced by 40% if the aortas were perfused with Staphylococcal Protein A, an Fc-binding protein, prior to injection of cells. No effect of Protein A on lymphocyte adhesion could be detected. An equally large reduction of monocyte adhesion was observed in segments initially perfused with IgG-depleted serum instead of native serum. Scanning and transmission electron microscopy indicated that monoctes adhered to intimal fibers, and also to injured endothelial cells. These data indicate that monocytes selectively adhere to defective endothelium, and that the adhesion is in part mediated via the Fc receptor. The significance of intimal monocytes for arterial repair and atherogenesis is discussed.