REGULATION OF THE METABOLISM OF LIPOPROTEIN-PROTEOGLYCAN COMPLEXES INHUMAN MONOCYTE-DERIVED MACROPHAGES

Studies were performed to evaluate the effect of several factors on th e metabolism of lipoprotein-proteoglycan complexes in human monocyte-d erived macrophages. In vivo apoB-lipoprotein-proteoglycan complex was isolated from human aorta fibrous-plaque lesions and low-density lipop rotein (LDL)-proteoglycan complex was formed in vitro. Degradation of LDL-proteoglycan complex and cholesteryl ester synthesis mediated by t he in vivo and in vitro complexes were lowest in freshly isolated mono cytes. With the maturation of monocytes into macrophages, there was a dramatic rise in both. The degradation of the complex and the resultan t stimulation of cholesterol esterification increased significantly wi th increasing cell density. Preincubation of macrophages in medium con taining lipoprotein cholesterol did not down-regulate the subsequent d egradation of LDL-proteoglycan complex. Macrophage-conditioned medium had a profound stimulatory effect on the degradation of LDL-proteoglyc an complex and cholesterol esterification by mature macrophages and fr eshly isolated monocytes. The conditioned medium lost its stimulatory activity after boiling, dialysis and trypsin digestion. Macrophage act ivation with phorbol ester and bacterial lipopolysaccharide resulted i n a marked suppression of the binding and degradation of the complex, as well as the complex-mediated cholesteryl ester synthesis. These res ults demonstrate that several factors regulate the metabolism of lipop rotein-proteoglycan complexes in human monocyte-derived macrophages.