Selective uptake of low-density lipoprotein-associated cholesteryl esters by human fibroblasts, human HepG2 hepatoma cells and J774 macrophages in culture.

High-density lipoprotein-(HDL) associated cholesteryl esters (CE) are taken up by hepatic and extrahepatic cells at a higher rate than HDL apolipoproteins. This selective uptake of HDL CE is independent from HDL particle uptake. For low-density lipoprotein (LDL), receptor-mediated endocytosis by cells is well established. In this study, the question was addressed if LDL-associated CE are also taken up by cells independently from LDL particles, i.e., selectively. Human LDL (d = 1.02-1.05 g/ml) was doubly radiolabeled with intracellularly trapped tracers: [125I]Tyramine-Cellobiose ([125I]TC) traced apolipoprotein B, [3H]cholesteryl oleyl ether ([3H]CEt) traced CE. The uptake of doubly radiolabeled LDL by normal and LDL receptor-negative human skin fibroblasts, human HepG2 hepatoma cells and murine J774 macrophages was investigated. Each cell type took up LDL particles as indicated by [125I]TC. However, in fibroblasts, HepG2 cells and J774 macrophages the rate of uptake for LDL-associated [3H]CEt was greater than that according to [125I]TC. These results indicate that extrahepatic and hepatic cells selectively take up LDL CE and this uptake is independent from LDL receptor-mediated endocytosis. Loading cells with cholesterol down-regulated selective uptake of LDL CE. In summary, human skin fibroblasts, human HepG2 cells and murine J774 macrophages selectively take up LDL CE, i.e., CE are taken up independently from LDL particles.