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

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.