1,25-DIHYDROXYVITAMIN-D-3-INDUCED HL-60 MACROPHAGES - REGULATION OF CHOLESTEROL AND LDL METABOLISM

Differentiation of human promyelocytic leukemic HL-60 cells with 1,25- dihydroxyvitamin D-3 (D-3) results in macrophages which exhibit specif ic and saturable receptor-mediated processing of both native and modif ied low density lipoprotein (LDL). Analysis of binding kinetics demons trated that macrophages bind LDL and acetyl-LDL with similar affinitie s, yet possess significantly different numbers of receptors (55 +/- 6 x 10(3) LDL receptors/cell vs. 79 +/- 7 x 10(3) acetyl-LDL receptors/c ell). D-3-induced HL-60 macrophages challenged with LDL or acetyl-LDL exhibited suppression of HMG-CoA reductase activity as well as a signi ficant induction in the incorporation of [C-14]oleate into cholesteryl ester compared with macrophages incubated with lipopretein depleted s erum. Maximum increases in ACAT activity were obtained in macrophages incubated with 25-hydroxycholesterol plus LDL or acetyl-LDL. The incre ase in ACAT activity in macrophages challenged with acetyl-LDL paralle led the increase in cellular cholesterol content and the increase of o il red O lipid stainable material, imparting the macrophages with a fo amy appearance. The data indicate that D-3-induced HL-60 macrophages a re a useful model for the study of lipoprotein-macrophage interactions as related to foam cell development and atherogenesis.