Binding and uptake of oxidized low density lipoprotein (LDL) by macrophage scavenger receptors are enhanced by substrate-bound fibronectin.
The uptake of oxidized low density lipoprotein (ox-LDL) by macrophages and the resulting accumulation of low density lipoprotein (LDL) lipids within the cells has been implicated in the pathogenesis of atherosclerosis. The effect of fibronectin (FN) on the binding and uptake of ox-LDL by macrophages was investigated using thioglycollate-induced mouse peritoneal macrophages. The ability of the macrophages to bind ox-LDL was assessed by the binding of mouse red blood cells (RBC) pre-coated with ox-LDL (ox-LDL-RBC) prepared in vitro to macrophages at 37 degrees C. The binding of ox-LDL-RBC to macrophages was significantly enhanced when the macrophages were plated on a FN-coated substrate. Similar enhancement was observed when the macrophages were plated on a substrate pre-coated with Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) peptide, an adhesive sequence of FN involved in binding to the cells, but not with the control Gly-Arg-Gly-Glu-Ser-Pro (GRGESP) peptide. The effect of FN was inhibited when GRGDSP, but not GRGESP, was present during the macrophage attachment to the FN-coated substrate, suggesting that the specific interaction of this sequence and the FN-receptor is responsible for the effect of FN. The addition of FN or GRGDSP in solution to the macrophage layers on an uncoated substrate was ineffective. Thus, attachment to a substrate is necessary for FN to be effective on the macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Beppu
M
M
Tokyo College of Pharmacy, Japan.
Hora
M
M
Watanabe
M
M
Kikugawa
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D016166:Free Radical Scavengers; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000302:isolation & purification / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism
D005353:Fibronectins; D016166:Free Radical Scavengers; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D012710:Serum Albumin, Bovine; D002784:Cholesterol