Receptor-mediated uptake of remnant lipoproteins by cholesterol-loaded human monocyte-macrophages.
Normal human monocyte-macrophages were cholesterol-loaded, and the rates of uptake and degradation of several lipoproteins were measured and compared to rates in control cells. Receptor activities for 125I-rabbit beta-very low density lipoproteins (beta-VLDL), 125I-human low density lipoprotein, and 125I-human chylomicrons were down-regulated in cholesterol-loaded cells; however, the rate of uptake and degradation of 125I-human chylomicron remnants was unchanged from control cells. Cholesterol-loaded alveolar macrophages from a Watanabe heritable hyperlipidemic rabbit, which lack low density lipoprotein receptors, showed receptor down-regulation for 125I-beta-VLDL but not for 125I-human chylomicron remnants. In addition to chylomicron remnants, apo-E-phospholipid complexes competed for 125I-chylomicron remnant uptake, but apo-A-I-phospholipid complexes did not. Chylomicrons competed for lipoprotein uptake in control cells but were not recognized under conditions of cholesterol loading. Chylomicron remnants and beta-VLDL were equally effective in competing for 125I-beta-VLDL and 125I-chylomicron remnant uptake in cholesterol-loaded macrophages. When normal human monocyte-macrophages were incubated in serum supplemented with chylomicron remnants, the cholesteryl ester content increased 4-fold over cells incubated in serum with low density lipoprotein added. We conclude: 1) specific lipoprotein receptor activity persists in cholesterol-loaded cells; 2) this receptor activity recognizes lipo-proteins (at least in part) by their apo-E content; and 3) cholesteryl ester accumulation can occur in monocyte-macrophages incubated with chylomicron remnants.
Van Lenten
B J
BJ
Fogelman
A M
AM
Jackson
R L
RL
Shapiro
S
S
Haberland
M E
ME
Edwards
P A
PA
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002914:Chylomicrons / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D008074:Lipoproteins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000502:physiology*; D018110:Receptors, Lipoprotein
D001057:Apolipoproteins E; D002914:Chylomicrons; D007457:Iodine Radioisotopes; D008074:Lipoproteins; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; D002784:Cholesterol