REGULATION OF THE METABOLISM OF LIPOPROTEIN-PROTEOGLYCAN COMPLEXES IN HUMAN MONOCYTE-DERIVED MACROPHAGES

Studies were performed to evaluate the effect of several factors on the metabolism of lipoprotein-proteoglycan complexes in human monocyte-derived macrophages. In vivo apoB-lipoprotein-proteoglycan complex was isolated from human aorta fibrous-plaque lesions and low-density lipoprotein (LDL)-proteoglycan complex was formed in vitro. Degradation of LDL-proteoglycan complex and cholesteryl ester synthesis mediated by the in vivo and in vitro complexes were lowest in freshly isolated monocytes. With the maturation of monocytes into macrophages, there was a dramatic rise in both. The degradation of the complex and the resultant stimulation of cholesterol esterification increased significantly with increasing cell density. Preincubation of macrophages in medium containing lipoprotein cholesterol did not down-regulate the subsequent degradation of LDL-proteoglycan complex. Macrophage-conditioned medium had a profound stimulatory effect on the degradation of LDL-proteoglycan complex and cholesterol esterification by mature macrophages and freshly isolated monocytes. The conditioned medium lost its stimulatory activity after boiling, dialysis and trypsin digestion. Macrophage activation with phorbol ester and bacterial lipopolysaccharide resulted in a marked suppression of the binding and degradation of the complex, as well as the complex-mediated cholesteryl ester synthesis. These results demonstrate that several factors regulate the metabolism of lipoprotein-proteoglycan complexes in human monocyte-derived macrophages.