1,25-Dihydroxyvitamin D3-induced HL-60 macrophages: regulation of cholesterol and LDL metabolism

Zeinab E. Jouni, Joy J. Winzerling, Donald J. McNamara

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Differentiation of human promyelocytic leukemic HL-60 cells with 1,25-dihydroxyvitamin D3 (D3) results in macrophages which exhibit specific and saturable receptor-mediated processing of both native and modified low density lipoprotein (LDL). Analysis of binding kinetics demonstrated that macrophages bind LDL and acetyl-LDL with similar affinities, yet possess significantly different numbers of receptors (55 ± 6 × 103 LDL receptors/cell vs. 79 ± 7 × 103 acetyl-LDL receptors/cell). D3-induced HL-60 macrophages challenged with LDL or acetyl-LDL exhibited suppression of HMG-CoA reductase activity as well as a significant induction in the incorporation of [14C]oleate into cholesteryl ester compared with macrophages incubated with lipoprotein depleted serum. Maximum increases in ACAT activity were obtained in macrophages incubated with 25-hydroxycholesterol plus LDL or acetyl-LDL. The increase in ACAT activity in macrophages challenged with acetyl-LDL paralleled the increase in cellular cholesterol content and the increase of oil red O lipid stainable material, imparting the macrophages with a foamy appearance. The data indicate that D3-induced HL-60 macrophages are a useful model for the study of lipoprotein -macrophage interactions as related to foam cell development and atherogenesis.

Original languageEnglish (US)
Pages (from-to)125-138
Number of pages14
JournalAtherosclerosis
Volume117
Issue number1
DOIs
StatePublished - Sep 1995

Keywords

  • 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase
  • AcylCoA cholesterol acyltransferase (ACAT)
  • HL-60 cells
  • LDL (apo B/E) receptor
  • Macrophages
  • Scavenger receptor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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