Atherosclerosis and inflammation - Mononuclear cell recruitment and adhesion molecules with reference to the implication of ICAM-1/LFA-1 pathway in atherogenesis

Recent investigations have reanimated the view that there exists a possible link between atherosclerosis and inflammation. Adhesion of monocytes as well as T lymphocytes to the arterial endothelial surface, followed by their migration into the subendothelial space is a hallmark for experimental animals fed an atherogenic diet. Human studies show identical features in the arterial wall to the animal models of atherosclerosis. The recruitment of leukocytes into areas of inflammation is mediated by interacting sets of cell adhesion molecules In atherosclerosis, focal expression of key adhesion molecules particularly triggered by plasma atherogenic lipoproteins has been detected, and these molecules may mediate the recruitment of mononuclear cells to the plaque. Among these adhesion molecules, ICAM-1, a protein of the Ig superfamily, and one of the ligands for LFA-1 have been suggested to play an important role in atherogenesis. In diet-induced hypercholesterolemic rats, we found that ICAM-1 expression is up-regulated mainly in lesion-prone areas of the aorta during the early stages of atherogenesis. Increased ICAM-1 expression was associated with a marked monocyte and T lymphocyte intimal recruitment. Further immunohistochemical studies have demonstrated that LFA-1 is expressed by more than 85% of macrophages in the lesions, and their presence therefore may point toward the involvement of the LFA-1 / ICAM-1 receptor ligand pathway in the recruitment of mononuclear cells in the lesions. In order to verify this hypothesis, systemic administration of blocking antibodies was attempted; injection of anti-ICAM-1 / LFA-1 monoclonal antibodies significantly reduced macrophage adherence and their emigration into the intima. Our current study suggests that ICAM-1 may act as an "athero-ELAM" for mononuclear cell intimal recruitment during atherogenesis. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.