Lipoprotein receptors of HL-60 macrophages. Effect of differentiation with tetramyristic phorbol acetate and 1,25-dihydroxyvitamin D3.
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.
Jouni
Z E
ZE
Department of Nutrition and Food Science, University of Arizona, Tucson 85721.
McNamara
D J
DJ
D000107:Acetylation; D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate