SELECTIVE UPTAKE OF HIGH-DENSITY LIPOPROTEIN-ASSOCIATED CHOLESTERYL ESTERS AND HIGH-DENSITY-LIPOPROTEIN PARTICLE UPTAKE BY HUMAN MONOCYTE-MACROPHAGES

High-density lipoprotein (HDL) cholesteryl esters (CE) are taken up by many cells without parallel uptake of HDL apolipoproteins. This selec tive uptake of HDL CE was investigated in human monocyte-derived macro phages (HMM). HDL3 (d = 1.125-1.21 g/ml) was labeled in its apolipopro tein A-1 moiety with I-125 and in its CE moiety with [H-3]cholesteryl oleyl ether. Cultured human monocyte-macrophages were incubated in the presence of doubly labeled HDL3 followed by determination of tracer u ptake. HMM took up HDL3 particles as indicated by the uptake of HDL3 a polipoproteins. Uptake of HDL3-associated CE tracer was in significant excess of that due to HDL3 particle uptake indicating selective uptak e of CE. Increased cell cholesterol due to preincubation with acetylat ed low-density lipoprotein (LDL) down-regulated selective uptake by HM M. According to several experimental approaches, selective uptake of H DL3 CE was independent from cell-secreted products, LDL receptor-media ted endocytosis or HDL3 retroendocytosis. The intracellular catabolism of HDL3 CE was investigated with HDL3 labeled in its CE moiety with [ H-3]cholesteryl oleate. The lysosomal inhibitor chloroquine had no eff ect on CE hydrolysis indicating that CE selectively taken up is hydrol yzed independently from lysosomes. In conclusion, HMM selectively take up HDL3-associated CE. The cellular mechanism of selective uptake is independent from endocytosis or retroendocytosis. Intracellularly, HDL 3 CE selectively taken up are catabolized independently from lysosomes .