Characterization of the low-density-lipoprotein-receptor-independent interaction of beta-very-low-density lipoprotein with rat and human parenchymal liver cells in vitro.
beta-Migrating very-low-density lipoprotein (beta-VLDL) is a cholesteryl-ester-enriched lipoprotein which under normal conditions is rapidly cleared by parenchymal liver cells. In this study the characteristics of the interaction of beta-VLDL with rat parenchymal cells, Hep G2 cells and human parenchymal cells are evaluated. The binding of beta-VLDL to these cells follows saturation kinetics (Bmax. respectively 117, 106 and 103 ng of beta-VLDL apoliprotein/mg of cell protein), with a relatively high affinity (Kd respectively for beta-VLDL of 10.7, 5.1 and 8.4 micrograms/ml). Competition studies of unlabelled beta-VLDL, low-density lipoprotein (LDL) or acetylated LDL with the binding of radiolabelled beta-VLDL indicate that a LDL-receptor-independent, Ca(2+)-independent, specific recognition site for beta-VLDL is present on rat and human parenchymal cells, whereas with Hep G2 cells or mouse macrophages beta-VLDL recognition is performed by the LDL receptor. The binding of beta-VLDL to Hep G2 cells was down-regulated by 89% by prolonged exposure to beta-VLDL, whereas for human parenchymal and rat parenchymal cells down-regulation of 44% and 20% respectively was observed. Studies with antibodies against the LDL receptor support the presence of a LDL-receptor-independent specific beta-VLDL recognition site on rat and human parenchymal cells. It is concluded that a LDL-receptor-independent recognition site for beta-VLDL is present on rat and human parenchymal liver cells. The presence of a LDL-receptor-independent recognition site on human parenchymal cells may mediate in vivo the uptake of beta-VLDL during consumption of a cholesterol-rich diet, when LDL receptors are down-regulated, thus protecting against the extrahepatic accumulation of the atherogenic beta-VLDL constituents.
De Water
R
R
Division of Biopharmaceutics, University of Leiden, The Netherlands.
Kamps
J A
JA
Van Dijk
M C
MC
Hessels
E A
EA
Kuiper
J
J
Kruijt
J K
JK
Van Berkel
T J
TJ
D000818:Animals; D000906:Antibodies; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008113:Liver Neoplasms; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D011973:Receptors, LDL / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000906:Antibodies; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL