Uptake of cholesterol-rich remnant lipoproteins by human monocyte-derived macrophages is mediated by low density lipoprotein receptors

The uptake and degradation of cholesterol-rich remnant lipo-proteins, referred to as 8-VLDL, are shown in the present study to be mediated by LDL receptors (apoB,E(LDL) recep-tors), not by unique Ol-VLDL receptors. Human blood mono-cytes cultured for 5-7 d bound apoB- and/or apoE-containing lipoproteins from different species with affinities equivalent to those demonstrated for the receptors on cultured human fibro-blasts. Low density lipoproteins competed effectively and com-pletely with '2I-#-VLDL for binding to and degradation by monocyte-derived macrophages. Specific polyclonal antibodies to bovine apoB,E(LDL) receptors abolished both LDL and #l-VLDL uptake by normal human monocyte-macrophages. Immunoblots of monocyte-macrophage extracts with these an-tibodies revealed a single protein in human macrophages with an apparent molecular weight identical to that of the apoB,E(LDL) receptor found on human fibroblasts. Like re-ceptors on cultured human fibroblasts, the apoB,E(LDL) re-ceptors on monocyte-macrophages responsible for '25I-j-VLDL and 125I-LDL uptake were efficiently down regulated by preincubation of the cells with fl-VLDL or LDL. Finally, monocyte-macrophages from seven homozygous familial hy-percholesterolemia subjects were unable to metabolize 6-VLDL or LDL, but demonstrated normal uptake of acetoace-tylated LDL. The classic apoB,E(LDL) receptors on human monocyte-macrophages thus mediate the uptake of I-VLDL by these cells