title: Serum amyloid P component binds to Fc gamma receptors and opsonizes particles for phagocytosis.
abstract: Serum amyloid P component (SAP) is a member of the pentraxin family of proteins. These proteins are characterized by cyclic pentameric structure, calcium-dependent ligand binding, and frequent regulation as acute-phase serum proteins. SAP is the serum precursor of the P component of amyloid. It binds to a broad group of molecules, including autoantigens, through a pattern recognition binding site. The related pentraxin, C-reactive protein (CRP), is a strong acute-phase reactant in man and an opsonin. We previously determined that the binding of CRP to leukocytes occurs through Fc receptors for IgG (FcgammaR). We now report that SAP also binds to FcgammaR and opsonizes particles for phagocytosis by human polymorphonuclear leukocytes (PMN). Specific, saturable binding of SAP to FcgammaRI, FcgammaRIIa, and FcgammaRIIIb expressed on transfected COS cells was detected using SAP-biotin and PE-streptavidin. Zymosan was used to test the functional consequences of SAP and CRP binding to FcgammaR. Both SAP and CRP bound to zymosan and enhanced its uptake by PMN. This enhanced phagocytosis was abrogated by treatment of PMN with wortmannin, a phosphatidylinositol-3 kinase inhibitor, or with piceatannol, a Syk inhibitor, consistent with uptake through FcgammaR. Treatment of PMN with phosphatidylinositol-specific phospholipase C to remove FcgammaRIIIb also decreased phagocytosis of SAP-opsonized zymosan, but not CRP-opsonized zymosan. These results suggest that SAP may function in host defense. In addition, as SAP binds to chromatin, a major immunogen in systemic lupus erythematosus, it may provide a clearance mechanism for this Ag through FcgammaR bearing cells.
authors.affiliation: Veterans Affairs Medical Center, 1501 San Pedro Southeast, Albuquerque, NM 87108, USA.
authors.forename: D
authors.initials: D
authors.lastname: Bharadwaj
authors.forename: C
authors.initials: C
authors.lastname: Mold
authors.forename: E
authors.initials: E
authors.lastname: Markham
authors.forename: T W
authors.initials: TW
authors.lastname: Du Clos
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D008863:Microspheres; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D009895:Opsonin Proteins / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism*; D000683:Serum Amyloid P-Component / Q000276:immunology / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D014162:Transfection; D010738:Type C Phospholipases / Q000494:pharmacology; D000077191:Wortmannin; D015054:Zymosan / Q000276:immunology / Q000378:metabolism
chemical_list: D000730:Androstadienes; D004791:Enzyme Inhibitors; D009895:Opsonin Proteins; D017452:Receptors, IgG; D000683:Serum Amyloid P-Component; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D015054:Zymosan; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D016650:Fluorescein-5-isothiocyanate; D000077191:Wortmannin