Characterization of the binding site on thioglycolate-stimulated mouse peritoneal macrophages that mediates the uptake of very low density lipoproteins.
Isolated mouse peritoneal macrophages that had been stimulated with thioglycolate were shown to take up and degrade normal human 125I-very low density lipoproteins (VLDL). Uptake occurred via a specific cell surface receptor which was shown to be 1) temperature-dependent, 2) calcium-dependent, and 3) susceptible to proteolytic digestion. The receptor-mediated uptake and degradation of VLDL markedly stimulated the synthesis and accumulation of triglyceride and cholesteryl ester within macrophages. The degradation of the protein and lipid portions of VLDL occurred within lysosomes. Competition studies showed that the binding site for VLDL was different from the receptor for normal low density lipoproteins or for acetylated low density lipoproteins but that there was cross competition with beta-VLDL. In addition, positive charges appeared to play an important role in the recognition of VLDL by their receptors since polyamines were able to markedly inhibit VLDL binding, degradation, and lipid accumulation while negatively charged compounds were without effects. These studies indicate that 1) stimulated mouse peritoneal macrophages possess specific receptors which recognize normal human VLDL and 2) the receptor-mediated uptake of VLDL results in the accumulation of triglyceride and cholesteryl ester within macrophages.
D000818:Animals; D001667:Binding, Competitive; D002122:Calcium Chloride / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011973:Receptors, LDL; D013864:Thioglycolates / Q000494:pharmacology*
D008079:Lipoproteins, VLDL; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D013864:Thioglycolates; C036053:VLDL receptor; C017487:2-mercaptoacetate; D002122:Calcium Chloride