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 lipoproteins, referred to as beta-VLDL, are shown in the present study to be mediated by LDL receptors (apoB,E(LDL) receptors), not by unique beta-VLDL receptors. Human blood monocytes 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 fibroblasts. Low density lipoproteins competed effectively and completely with 125I-beta-VLDL for binding to and degradation by monocyte-derived macrophages. Specific polyclonal antibodies to bovine apoB,E(LDL) receptors abolished both LDL and beta-VLDL uptake by normal human monocyte-macrophages. Immunoblots of monocyte-macrophage extracts with these antibodies 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 receptors on cultured human fibroblasts, the apoB,E(LDL) receptors on monocyte-macrophages responsible for 125I-beta-VLDL and 125I-LDL uptake were efficiently down regulated by preincubation of the cells with beta-VLDL or LDL. Finally, monocyte-macrophages from seven homozygous familial hypercholesterolemia subjects were unable to metabolize beta-VLDL or LDL, but demonstrated normal uptake of acetoacetylated LDL. The classic apoB,E(LDL) receptors on human monocyte-macrophages thus mediate the uptake of beta-VLDL by these cells.
Koo
C
C
Gladstone Foundation Laboratories for Cardiovascular Disease, Department of Pathology, University of California, San Francisco 94140-0608.
Wernette-Hammond
M E
ME
Garcia
Z
Z
Malloy
M J
MJ
Uauy
R
R
East
C
C
Bilheimer
D W
DW
Mahley
R W
RW
Innerarity
T L
TL
D000328:Adult; D000906:Antibodies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000378:metabolism*; D015243:Cholesterol, VLDL; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D007118:Immunoassay; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism*; D011973:Receptors, LDL / Q000032:analysis / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D015243:Cholesterol, VLDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D002784:Cholesterol