A Secretory Product of Human Monocyte-derived Macrophages Stimulates Low Density Lipoprotein Receptor Activity in Arterial Smooth Muscle Cells and Skin Fibroblasts

The ability of macrophages to influence the metabolism of native low density lipoprotein by arterial smooth muscle cells was evaluated using cultured human monocyte-derived macrophages. Macrophage-conditioned medium stimulated the binding and degradation of low density lipoprotein by cultured arterial smooth muscle cells and skin fibroblasts. Sterol synthesis also was stimulated by macrophage-conditioned medium as was cholesterol esterification in the presence of high concentrations of low density lipoprotein. These findings suggest that macrophages secrete a factor that enhances the activity of the low density lipoprotein receptor. Low density lipoprotein degradation by arterial smooth muscle cells also was enhanced by macrophage-conditioned medium in the presence of high concentrations of low density lipoproteins in the medium. The macrophage factor that stimulates low density lipoprotein metabolism is stable to freezing, is inactivated by acid hydrolysis, tryptic digestion, and boiling, and is of large molecular weight (greater than 12,000 to 14,000 daltons). Modulation of arterial smooth muscle cell metabolism of low density lipoprotein by a macrophage secretory product may be of importance in the pathogenesis of atherosclerosis.