Serum amyloid P component binds to Fc gamma receptors and opsonizes particles for phagocytosis

Serum amyloid P component (SAP) is a member of the pentraxin family of prot eins. These proteins are characterized by cyclic pentameric structure, calc ium-dependent ligand binding, and frequent regulation as acute-phase serum proteins. SAP is the serum precursor of the P component of amyloid. It bind s 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 deter mined that the binding of CRP to leukocytes occurs through Fe receptors for IgG (Fc gammaR). We now report that SAP also binds to Fc gammaR and opsoni zes particles for phagocytosis by human polymorphonucIear leukocytes (PMN). Specific, saturable binding of SAP to FcRI, FcRIIa, and Fc gamma RIIIb exp ressed on transfected COS cells was detected using SAP-biotin and PE-strept avidin. Zymosan was used to test the functional consequences of SAP and CRP binding to Fc gammaR. Both SAP and CRP bound to zymosan and enhanced its u ptake by PMN. This enhanced phagocytosis was abrogated by treatment of PMN with wortmannin, a phosphatidylinositol-3 kinase inhibitor, or with piceata nnol, a Syk inhibitor, consistent with uptake through FcR. Treatment of PMN with phosphatidylinositol-specific phospholipase C to remove Fc gamma RIII b also decreased phagocytosis of SAP-opsonized zymosan, but not CRP-opsoniz ed zymosan. These results suggest that SAP may function in host defense. In addition, as SAP binds to chromatin, a major immunogen in systemic lupus e rythematosus, it may provide a clearance mechanism for this Ag through Fc g ammaR bearing cells. The Journal of Immunology, 2001.