PROTEOGLYCANS PRODUCED BY CHOLESTEROL-ENRICHED MACROPHAGES BIND PLASMA LOW-DENSITY-LIPOPROTEIN

Proteoglycans (PG) produced by [S-35]sulfate and [H-3]serine labeled cultures of cholesterol-enriched macrophages obtained from atherosclerosis-susceptible White Carneau (WC) and -resistant Show Racer (SR) pigeons were characterized and assessed for their capacity to bind low density lipoprotein (LDL). The majority of S-35-labeled PG was released into the culture media in both WC and SR macrophage cultures and consisted of large and small size PG as determined by Sepharose CL-4B chromatography. Large PG were identified as chondroitin sulfate-PG comprised of 4-sulfated disaccharides whereas small PG consisted of primarily 4-sulfated chondroitin sulfate-PG and lesser amounts of heparin sulfate-PG. Experiments demonstrated that 32-34% of S-35-labeled large PG and 86-93% of small PG bound to LDL-substituted Sepharose. Interactions between PG and LDL-substituted Sepharose were inhibited in the presence of heparin or soluble LDL. Glycosaminoglycans derived from macrophage PG had a decreased binding affinity demonstrating the importance of an intact PG. The results suggest that macrophage PG may facilitate trapping of LDL in the intimal intima and promote foam cell formation through a mechanism involving the uptake of PG-LDL complexes.