Receptor-mediated binding of the acute-phase reactant mouse serum amyloid P-component (SAP) to macrophages.
Serum amyloid P-component (SAP) is a major acute phase protein of mice which we have previously shown increases the bactericidal activity of elicited, inflammatory macrophages (M phi). The presence of specific receptors for mouse SAP on M phi was demonstrated and the receptor-ligand (SAP) interaction characterized. Purified 125I-labeled mouse SAP binds to elicited M phi with the characteristics of a receptor-mediated event, i.e., the binding was saturable, specific, and reversible. A single type of receptor population was detected with an affinity of 5 x 10(-8) M (KD) and the calculated number of receptor sites per cell was approximately 10(5). Binding of SAP to M phi required Ca2+ or Mg2+ and was inhibited at a pH less than or equal to 5.6. Activated M phi from mice given BCG bind less SAP than nonactivated M phi. Activation of M phi with mouse interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS) also decreased their SAP binding capacity. SAP is a glycosylated protein with a high mannose content; therefore mannose and other sugars were tested for inhibition of binding. Specific binding of SAP was inhibited by less than 1 mM concentrations of mannose 6-P, mannose 1-P, and mannose; however, other monosaccharides did not inhibit the binding. Removal of the oligosaccharide from SAP with an endoglycosidase specific for N-linked carbohydrate reduced the binding of SAP to M phi. The pattern of inhibition by sugars, the divalent cation requirement, and the sensitivity to low pH indicate that the receptor binding SAP is the cation-dependent mannose 6-P receptor, or a closely related receptor. The results suggest that SAP may alter or trigger M phi functions associated with inflammation by binding to glycoprotein receptors.
D000818:Animals; D001667:Binding, Competitive; D002241:Carbohydrates / Q000494:pharmacology; D002413:Cations, Divalent / Q000502:physiology; D005947:Glucose / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007371:Interferon-gamma / Q000494:pharmacology; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D010766:Phosphorylation; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism*; D018000:Receptors, Peptide; D000683:Serum Amyloid P-Component / Q000302:isolation & purification / Q000378:metabolism*; D013045:Species Specificity
D002241:Carbohydrates; D002413:Cations, Divalent; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D000683:Serum Amyloid P-Component; D007371:Interferon-gamma; D005947:Glucose; D008358:Mannose