MODIFIED LOW-DENSITY-LIPOPROTEIN AND CYTOKINES MEDIATE MONOCYTE ADHESION TO SMOOTH-MUSCLE CELLS

Monocyte adhesion to the arterial wall is a key event in the atheroscl erotic process. We studied the interactions between human coronary art erial intimal smooth muscle cells (SMCs) and monocytes by examining (i ) whether SMCs mediate monocyte adhesion when stimulated by oxidativel y modified low density lipoprotein (LDL) or by the cytokines TNF alpha and IL-1, and (ii) the role of the adhesion molecules VCAM-1 and ICAM -1 (vascular cell and intercellular adhesion molecule, respectively) i n this process. Preincubation of SMCs with both TNF alpha and IL-1 cau sed a significant 2-fold increase in VCAM-1 and ICAM-1 expression and a more than 9-fold increase in monocyte adhesion. The latter was signi ficantly inhibited (by 1/3) by neutralising antibodies to VCAM-1 and I CAM-1. Modified LDL also induced a significant 3-fold increase in mono cyte adhesion to SMCs, but did not induce VCAM-1 or ICAM-1 expression, nor was this adhesion inhibited by neutralising antibodies to VCAM-1 or ICAM-1. Oxidatively modified LDL, like the proinflammatory cytokine s TNF-alpha and IL-1, has the ability to enhance monocyte adhesion to human SMCs in vitro. LDL-induced monocyte adhesion to SMCs is distinct from that induced by TNF alpha and IL-1 in its lack of dependence on the classical adhesion pathways involving smooth muscle VCAM-1 and ICA M-1. SMCs are identified as a new cell population which may play an ac tive role in recruiting monocytes to the arterial intima and atheroscl erotic plaque.