title: A macrophage receptor that recognizes oxidized low density lipoprotein but not acetylated low density lipoprotein.
abstract: The formation of cholesterol-loaded macrophage foam cells in arterial tissue may occur by the uptake of modified lipoproteins via the scavenger receptor pathway. The macrophage scavenger receptor, also called the acetylated low density lipoprotein (Ac-LDL) receptor, has been reported to recognize Ac-LDL as well as oxidized LDL species such as endothelial cell-modified LDL (EC-LDL). We now report that there is another class of macrophage receptors that recognizes EC-LDL but not Ac-LDL. We performed assays of 0 degrees C binding and 37 degrees C degradation of 125I-Ac-LDL and 125I-EC-LDL by mouse peritoneal macrophages. Competition studies showed that unlabeled Ac-LDL could compete for only 25% of the binding and only 50% of the degradation of 125I-EC-LDL. Unlabeled EC-LDL, however, competed for greater than 90% of 125I-EC-LDL binding and degradation. Unlabeled Ac-LDL was greater than 90% effective against 125I-Ac-LDL; EC-LDL competed for about 80% of 125I-Ac-LDL binding and degradation. Copper-oxidized LDL behaved the same as EC-LDL in all the competition studies. Copper-mediated oxidation of Ac-LDL produced a superior competitor which could now displace 90% of 125I-EC-LDL binding. After 5 h at 37 degrees C in the presence of ligand, macrophages accumulated six times more cell-associated radioactivity from 125I-EC-LDL than from 125I-Ac-LDL, despite approximately equal amounts of degradation to trichloroacetic acid-soluble products, which may imply different intracellular processing of the two lipoproteins. Our results suggest that 1) there is more than one macrophage "scavenger receptor" for modified lipoproteins; and 2) oxidized LDL and Ac-LDL are not identical ligands with respect to macrophage recognition and uptake.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093.
authors.forename: C P
authors.initials: CP
authors.lastname: Sparrow
authors.forename: S
authors.initials: S
authors.lastname: Parthasarathy
authors.forename: D
authors.initials: D
authors.lastname: Steinberg
mesh_terms: D000107:Acetylation; D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000302:isolation & purification / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D011817:Rabbits; D011973:Receptors, LDL / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D011973:Receptors, LDL