Cholesteryl ester accumulation in macrophages resulting from receptor-mediated uptake and degradation of hypercholesterolemic canine β-very low density lipoproteins

J. L. Goldstein, Y. K. Ho, M. S. Brown, T. L. Innerarity, R. W. Mahley

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Abstract

The synthesis and accumulation of cholesteryl esters by monolayers of mouse peritoneal macrophages was stimulated 20- to 160-fold by incubations with β-migrating very low density lipoproteins (β-VLDL, density<1.006g/ml) isolated from the plasma of cholesterol-fed dogs. Three other cholesterol-rich lipoprotein fractions obtained from the plasma of the same hypercholesterolemic dogs, including low density lipoprotein (LDL), cholesterol-induced high density lipoprotein (HDL(c)), and apo-E HDL(c), had little to no stimulatory effect. Plasma VLDL (density<1.006g/ml) from normal dogs did not increase cholesteryl ester formation in macrophages. The enhancement in cholesteryl ester synthesis and accumulation by hypercholesterolemic canine β-VLDL was due to the presence of a high affinity binding site on the macrophage cell surface that mediated the uptake and lysosomal degradation of the β-VLDL. Competition studies with fucoidin and dextran sulfate indicated that the receptor for canine β-VLDL was different from that previously described for human acetylated low density lipoprotein (acetyl-LDL). Prior incubation of macrophage monolayers with either unlabeled canine β-VLDL or human acetyl-LDL, both of which raised the cellular content of cholesteryl esters, reduced the ability of the cells to degrade 125I-labeled β-VLDL, suggesting that the receptor for β-VLDL is subject to regulation. The current findings indicate: (1) that macrophages possess a high affinity receptor that recognizes one of the four cholesterol-rich lipoproteins present in the plasma of cholesterol-fed dogs, β-VLDL, and 2) that the receptor-mediated ingestion of β-VLDL leads to cholesteryl ester deposition in these cells.

Original languageEnglish (US)
Pages (from-to)1839-1848
Number of pages10
JournalJournal of Biological Chemistry
Volume255
Issue number5
StatePublished - Nov 10 1980

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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