Degradation of low density lipoprotein . dextran sulfate complexes associated with deposition of cholesteryl esters in mouse macrophages.

The uptake and degradation of ‘251-labeled human plasma low density lipoprotein (lZ51-LDL) by mouse peritoneal macrophages was increased markedly by the addition of high molecular weight dextran sulfate (Mr = 500,000) to the incubation medium. The dextran sulfate and the ‘%LDL formed a complex that was taken up and degraded with saturation kinetics, suggesting a requirement for a specific surface binding site. Degradation of the lz51-LDL component of the complex was inhibited by the lysosomotropic agent chloroquine. Uptake and degradation of the ‘251-LDL*dextran sulfate complex were abolished by spermine and spermidine, two polyamines that disrupted the complex. Competition studies with polyinosinic acid and fucoidin suggested that the LDLedextran sulfate complex was recognized by a surface binding site that was different from the previously described site that mediates the uptake and degradation of acetylated LDL. Low molecular weight dextran sulfate (M= = 40,000) and a number of naturally occurring low molecular weight-sulfated glycosaminoglycans, including heparin and dermatan sulfate, did not stimulate LDL uptake or degradation. The dextran sulfate-stimulated degradation of LDL enhanced the rate of cholesteryl ester formation in the macrophages, with a consequent marked increase in the cellular content of free and esterified cholesterol. These experiments indicate that macrophages have the capacity to ingest large amounts of LDL in association with high molecular weight-sulfated polysaccharides and that this ingestion leads to cholesteryl ester deposition in these cells.