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Arteriosclerosis, Thrombosis, and Vascular Biology. 1991;11:995-1006

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Arteriosclerosis and Thrombosis, Vol 11, 995-1006, Copyright © 1991 by American Heart Association

ARTICLES

Lipoprotein receptors of HL-60 macrophages. Effect of differentiation with tetramyristic phorbol acetate and 1,25-dihydroxyvitamin D3

ZE Jouni and DJ McNamara
Department of Nutrition and Food Science, University of Arizona, Tucson 85721.

The human promyelocytic leukemic cell line HL-60 is a unique model for studies of the effects of macrophage differentiation on the expression and regulation of lipoprotein receptors. Undifferentiated HL-60 cells express a regulated low density lipoprotein (LDL) receptor and lack the acetylated LDL (acetyl-LDL) scavenger receptor. HL-60 macrophages differentiated with tetramyristic phorbol acetate failed to degrade LDL and acetyl-LDL via receptor-mediated processes. Differentiation with 1,25-dihydroxyvitamin D3 (D3) induced macrophages exhibiting specific saturable receptors for LDL and acetyl-LDL. The LDL receptor of D3- induced macrophages was found to exhibit specificity for apolipoprotein B- and E-containing lipoproteins, to be calcium dependent, and to be inhibited by pronase and chloroquine. Maximal degradation of acetyl-LDL was achieved within 2 days of D3 treatment and was specific for acetyl- LDL, was calcium independent, was inhibited by chloroquine, and was sensitive to pronase and fucoidin treatment. Incubation of D3-induced macrophages with LDL or acetyl-LDL resulted in reductions in sterol synthesis and receptor-mediated degradation of LDL; the scavenger receptor pathway was unaltered. These results demonstrate that D3- induced HL-60 macrophages exhibit patterns of sterol and lipoprotein metabolism and regulation that make them a useful model system for in vitro studies of lipoprotein-macrophage interactions related to foam cell development and atherogenesis.


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[Abstract] [Full Text] [PDF]


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