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Research report| Volume 117, ISSUE 1, P125-138, September 1995

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

  • Zeinab E. Jouni
    Footnotes
    Affiliations
    Department of Nutritional Sciences and Interdisciplinary Nutritional Sciences Program, 309 Shantz Building, The University of Arizona, Tucson, AZ 85721, USA
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  • Joy J. Winzerling
    Footnotes
    Affiliations
    Department of Nutritional Sciences and Interdisciplinary Nutritional Sciences Program, 309 Shantz Building, The University of Arizona, Tucson, AZ 85721, USA
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  • Donald J. McNamara
    Correspondence
    Corresponding author. Tel.: +1 602 621 1971; Fax: +1 602 621 9446.
    Affiliations
    Department of Nutritional Sciences and Interdisciplinary Nutritional Sciences Program, 309 Shantz Building, The University of Arizona, Tucson, AZ 85721, USA
    Search for articles by this author
  • Author Footnotes
    1 Current address: Department of Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
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      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.

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