EFFECT OF LOW-DENSITY-LIPOPROTEIN ON MONOCYTE ADHESIVENESS TO ENDOTHELIAL-CELLS INVITRO

Adhesion of monocytes to the endothelium is an early event in the development of atherosclerosis. The possibility that low density lipoproteins enhance this process by activating monocytes was investigated using an in vitro adhesion test on endothelial cell monolayer cultures. Preincubation of monocytes with low density lipoprotein (LDL) (100 mug LDL protein/l x 10(6) cells/ml) for 15 min induced a 70% increase in adhesion to endothelial cells with a maximal effect at 100 mug LDL protein/ml and a short latency of effect (2 min). Anti-LDL receptor antibody, which inhibited LDL binding, blocked this activation. The LDL effect appeared to depend on receptor binding of LDL rather than on receptor-mediated endocytosis, since preincubation of monocytes with LDL at either 4-degrees-C or 37-degrees-C resulted in the same stimulation of adhesion. A cytofluorimetric study using integrin monoclonal antibodies (MAbs) against CD18 and CD11b did not reveal any increase in expression of the integrins on the surface of LDL-activated monocytes. However, a 30-min preincubation of monocytes with anti-CD18 abolished the LDL-activated adhesion. These results indicate that LDL induces a rapid activation of monocyte adhesiveness to endothelial cells. This effect appears to be mediated by interaction of LDL with its receptor rather than LDL-receptor complex internalization or integrin membrane mobilization from intracellular pools. The integrin system nevertheless appears to be involved.