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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.
Keywords
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Article info
Publication history
Accepted:
March 14,
1995
Received in revised form:
March 9,
1995
Received:
December 20,
1994
Identification
Copyright
© 1995 Published by Elsevier Inc.