Recognition sites on rat liver cells for oxidatively modified beta-very low density lipoproteins.
The in vivo fate of beta-very low density lipoproteins (beta-VLDLs) was investigated after Cu(2+)-mediated oxidative modification (Ox-beta-VLDL). Ox-beta-VLDL may be physiologically relevant under conditions of defective VLDL removal by the liver (type III hyperlipoproteinemia) or overloading of the remnant receptor (high cholesterol feeding). On oxidation of beta-VLDL, the kinetics of its removal from the blood and uptake by the liver are unchanged. However, in contrast to beta-VLDL, which is recognized by the remnant receptor of parenchymal cells, liver uptake of Ox-beta-VLDL is mediated mainly by Kupffer cells (65% of liver-associated radioactivity). In vitro competition studies show that the cell association and degradation of iodine-125-labeled Ox-beta-VLDL by both liver endothelial and Kupffer cells are only marginally competed for by acetylated LDL (10-20%), while an efficient blockade is noted with Ox-beta-VLDL, oxidized low density lipoproteins, or polyinosinic acid (80-90%). The capacity of Kupffer cells to associate with and degrade 125I-Ox-beta-VLDL appears to be twofold higher than for endothelial cells. It is concluded that on oxidation of beta-VLDL, the recognition system responsible for the uptake of beta-VLDL from the blood circulation is shifted from the remnant receptor to a specific oxidized-lipoprotein receptor. The efficiency of the scavenger activity on Kupffer cells will then form the protection system against the prolonged circulation of these atherogenic lipoproteins in the blood.
de Rijke
Y B
YB
Division of Biopharmaceutics, Sylvius Laboratories, University of Leiden, The Netherlands.
Hessels
E M
EM
van Berkel
T J
TJ
D000818:Animals; D001667:Binding, Competitive; D003300:Copper; D004727:Endothelium / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D007728:Kupffer Cells / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D011973:Receptors, LDL / Q000378:metabolism
D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; C036053:VLDL receptor; D003300:Copper