Very low density lipoproteins promote triglyceride accumulation in macrophages.
Incubation of mouse peritoneal macrophages with very low density lipoproteins (VLDL) from normal rats or rhesus monkeys markedly increased the levels of intracellular triglycerides by 10- to 56-fold and was accompanied by the production of oil red O positive vacuoles. The stimulation of triglyceride accumulation in macrophages was time- and concentration-dependent and was specific for VLDL. Three possible mechanisms for the VLDL-stimulated triglyceride accumulation in macrophages were explored: receptor-mediated uptake, action of lipoprotein lipase, and phagocytosis. Macrophage uptake and degradation of 125I-monkey and rat VLDL demonstrated saturable and nonsaturable components. Uptake of 125I-VLDL could be inhibited by unlabeled normal VLDL, although hyperlipemic VLDL was more effective. HDL did not compete to a significant extent. Heparin released lipoprotein lipase-like activity from peritoneal macrophages. Addition of heparin with VLDL resulted in a greater, more rapid elevation in intracellular triglycerides, which was partially inhibited by albumin. Free fatty acid and Intralipid also produced triglyceride accumulation in macrophages. The data showed that all three of the mechanisms examined could contribute to the metabolism of VLDL by macrophages and cause the production of triglyceride-rich cells with a "foamy" appearance, although the evidence suggested that the action of lipoprotein lipase was probably the most important in this process.
D000818:Animals; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000494:pharmacology*; D008253:Macaca mulatta; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013268:Stimulation, Chemical; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
D002788:Cholesterol Esters; D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D012710:Serum Albumin, Bovine; D006493:Heparin; D008071:Lipoprotein Lipase