Accumulation of cholesteryl ester and lipid droplets in macrophages after uptake of cholesterol-rich necrotic products.
The prevalence of degenerated cells in the thickened intima of cholesterol-fed animals suggested that necrotic regions might become a focus for lesion development by attracting histiocytes or monocytes. We propose that cholesterol-rich necrotic products scavenged by macrophages incite the accumulation of cholesteryl ester and the formation of cholesteryl ester droplets. The feasibility of this hypothesis was tested with readily available materials, namely, lung macrophages and plasma membrane vesicles (PMV) released from dying cholesterol-rich and normal hepatocytes. PMV from cholesterol-rich hepatocytes contained 30-fold more cholesteryl ester than PMV from normal hepatocytes. Degradation of 125I-PMV to trichloroacetic acid-soluble products by macrophages was fourfold higher than that of 125I-acetylated low density lipoprotein (acetyl-LDL) at 100 micrograms/ml of ligand in the incubation medium. Within this concentration range, degradation of PMV increased almost linearly with increasing concentrations of PMV, while the degradation of acetyl-LDL followed a saturation curve. Cholesterol-rich PMV increased the cholesteryl ester content of macrophages fourfold and augmented the incorporation of oleate threefold relative to normal PMV. These studies were extended to aortic smooth muscle cells. As with hepatocyte-PMV, smooth muscle cell-PMV was internalized and degraded by macrophages. The results suggested that cholesterol-rich necrotic materials could play a significant role in atherogenesis.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000648:ultrastructure; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009336:Necrosis; D010587:Phagocytosis; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; C032629:acetyl-LDL; D002784:Cholesterol