Recognition of sialosaccharide chains of glycophorin on damaged erythrocytes by macrophage scavenger receptors.

Binding of mouse erythrocytes oxidized in vitro mildly with diamide, periodate or ADP/Fe3+, and the erythrocytes incubated in vitro in a serum-free medium for 12 h (in vitro aged erythrocytes) to mouse peritoneal macrophages was effectively inhibited by isolated glycophorin A, a major sialoglycoprotein of human erythrocyte membrane existing as oligomers in solution, and some of known ligands for macrophage scavenger receptors such as maleyl-BSA, dextran sulfate, fucoidan and polyinosinic acid. Binding of oxidized low density lipoprotein (ox-LDL) to macrophages was inhibited by glycophorin A as well as the known ligands. When the sialyl residues of the saccharide chains of glycophorin A were cleaved by neuraminidase, or the polypeptide of glycophorin A was digested by Pronase, which would destroy its oligomeric forms, the inhibitory effect of glycophorin A was decreased, suggesting that isolated glycophorin A binds to scavenger receptors depending on its sialyl residues and oligomeric structure. Glycopeptides prepared from the N-terminal region of glycophorin A containing most of the sialosaccharide chains of the molecule inhibited the binding of ox-LDL although the potency was lower than that of glycophorin A. N-Acetylneuraminic acid at a high concentration also inhibited the ox-LDL binding. Uptake and degradation of 125I-labeled ox-LDL by macrophages was inhibited by glycophorin A, N-acetylneuramin lactose, as well as the known ligands. 125I-labeled glycophorin A bound to macrophages, and the binding was inhibited by the unlabeled glycophorin A and the known ligands. Inhibitory activity of the unlabeled glycophorin A against the labeled glycophorin A-binding was lowered by neuraminidase and Pronase treatment. These results suggest that oxidized and in vitro aged mouse erythrocytes are recognized by scavenger receptors of mouse peritoneal macrophages, and the cell surface components recognized are sialosaccharide chains of glycophorin, possibly glycophorin A counterpart of mouse erythrocytes which clustered or aggregated in the membrane. The finding indicates that the cell surface sialosaccharides can be ligands for scavenger receptors when cells undergo denaturation by oxidative stress or other damaging effects.