Specific interaction of oxidized low-density lipoprotein with macrophage-derived foam cells isolated from rabbit atherosclerotic lesions

Interaction of oxidized LDL (OxLDL) with macrophage-derived foam cells is o ne of the key events in the development and progression of atherosclerosis. To study this interaction, macrophage-derived foam cells were isolated fro m rabbit atherosclerotic lesions and the expression of scavenger receptors for OxLDL was examined. Atherosclerosis was induced in rabbits by denudatio n of the large arteries, followed by a hypercholesteremic diet. Macrophage- derived foam cells, characterized by immunostaining with an RAM-11 antibody (a macrophage marker), contained a high content of intracellular Lipid. Ma ximal binding of radiolabeled OxLDL to isolated macrophage-derived foam cel ls (1652+/-235 ng I-125-OxLDL/mg of cell protein) was 20-fold higher compar ed with B-max values of monocytes. Levels of association of OxLDL to macrop hage-derived foam cells isolated from atherosclerotic lesions 12 weeks afte r denudation were >3-fold higher compared with the levels expressed by macr ophage-derived foam cells isolated after 6 weeks. Association of I-125-OxLD L could be completely blocked by OxLDL, and partially by acetylated LDL and polyinosinic acid, indicating the presence of a specific binding site for OxLDL on macrophage-derived foam cells. The induction of scavenger receptor s for OxLDL on macrophage-derived foam cells during the development of athe rosclerosis, as described in this study, may facilitate the lipid accumulat ion in macrophage-derived foam cells, as observed in advanced atherosclerot ic lesions.