Rat liver Kupffer and endothelial cells express different binding proteins for modified low density lipoproteins. Kupffer cells express a 95-kDa membrane protein as a specific binding site for oxidized low density lipoproteins.
The liver is the major organ responsible for the uptake of oxidized low density lipoproteins (Ox-LDL) from the blood circulation with Kupffer cells as major cellular uptake site. Candidate binding proteins for Ox-LDL on membranes from Kupffer and endothelial liver cells were identified with ligand blots. Under nonreducing conditions, a major binding protein with an estimated molecular mass of 95 kDa and a minor stained protein of 220 kDa were detected on Kupffer cell membranes, while endothelial cell membranes expressed only a 220-kDa binding protein. Both the 95-kDa protein of Kupffer cell membranes and the 220-kDa protein of endothelial membranes displayed saturable binding of 125I-Ox-LDL with a Kd of 15 and 5 micrograms/ml, respectively. LDL was a weak competitor for the binding of 125I-Ox-LDL to the 95-kDa protein, while the degree of competition appeared to be dependent on the oxidation grade of LDL with a complete competition with LDL oxidized for 20 h with 10 microM Cu2+. We conclude that the 95-kDa binding protein, highly concentrated on rat Kupffer cells, forms the most likely candidate for mediating the in vivo uptake of Ox-LDL from the blood circulation.
de Rijke
Y B
YB
Division of Biopharmaceutics, Leiden-Amsterdam Center for Drug Research, Sylvius Laboratories, University of Leiden, The Netherlands.
van Berkel
T J
TJ
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008970:Molecular Weight; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C032629:acetyl-LDL