Selective uptake of high-density lipoprotein-associated cholesteryl esters and high-density lipoprotein particle uptake by human monocyte-macrophages

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High-density lipoprotein (HDL) cholesteryl esters (CE) are taken up by many cells without parallel uptake of HDL apolipoproteins. This selective uptake of HDL CE was investigated in human monocyte-derived macrophages (HMM). HDL 3 ( d= 1.125-1.21 g/ml) was labeled in its apolipoprotein A-I moiety with 125I and in its CE moiety with [ 3H]cholesteryl oleyl ether. Cultured human monocyte-macrophages were incubated in the presence of doubly labeled HDL 3 followed by determination of tracer uptake. HMM took up HDL 3 particles as indicated by the uptake of HDL 3 apolipoproteins. Uptake of HDL 3-associated CE tracer was in significant excess of that due to HDL 3 particle uptake indicating selective uptake of CE. Increased cell cholesterol due to preincubation with acetylated low-density lipoprotein (LDL) down-regulated selective uptake by HMM. According to several experimental approaches, selective uptake of HDL 3 CE was independent from cell-secreted products, LDL receptor-mediated endocytosis or HDL 3 retroendocytosis. The intracellular catabolism of HDL 3 CE was investigated with HDL 3 labeled in its CE moiety with [ 3H]cholesteryl oleate. The lysosomal inhibitor chloroquine had no effect on CE hydrolysis indicating that CE selectively taken up is hydrolyzed independently from lysosomes. In conclusion, HMM selectively take up HDL 3-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.