Serum Amyloid P Component Binds to Fcγ 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 (FcγR). We now report that SAP also binds to FcγR and opsonizes particles for phagocytosis by human polymorphonuclear leukocytes (PMN). Specific, saturable binding of SAP to FcγRI, FcγRIIa, and FcγRIIIb 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 FcγR. 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 FcγR. Treatment of PMN with phosphatidylinositol-specific phospholipase C to remove FcγRIIIb 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 FcγR bearing cells.

Central and Systemic Endotoxin Challenges Exacerbate the Local Inflammatory Response and Increase Neuronal Death during Chronic Neurodegeneration

“…Acute-phase reactant gene expression following LPS challenge was generally similar in ME7 and NBH animals, but PTX3 was highly induced by LPS in prion-diseased mice compared with control animals. PTX3 is a member of the pentraxins, which are thought to opsonize apoptotic cells, pathogens, and debris for phagocytosis by Fc␥ receptor-expressing cells (Bharadwaj et al, 2001;Mold et al, 2002a,b). Like C-reactive protein, PTX3 has been shown to exert control over the degree of activation of macrophages: PTX3 overexpressing macrophages produce more robust responses to LPS challenges than controls (Dias et al, 2001).…”

Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic trimer with new recognition and effector faces

“…Short-chain pentraxins are soluble pattern recognition receptors produced in the liver in response to inflammatory signals and subsequently act as multifunctional antibodies in the innate immune system (Ganapathi et al, 1991;Lu et al, 2012). PTXs also trigger the complement system via the classical complement pathway through C1q Volanakis and Kaplan, 1974) and increase pathogen clearance via phagocytosis (Bharadwaj et al, 2001). Short-chain pentraxins are involved in acute-phase response (APR) and recognise various pathogenic bacteria or cellular debris in a characteristic calcium-dependent manner (Abernethy and Avery, 1941;Thompson et al, 1999).…”

Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine

“…25,26 Therefore, we hypothesized that the hSAP in plasmid-protein complexes might facilitate the adsorption and phagocytosis of DNA when hSAP binds its membrane receptors on monocytes. To test this hypothesis, we first confirmed the monocyte-binding ability of the hSAP-DNA complex using the human promonocytic cell line THP-1-cell line-derived macrophages (MDMs) as a cell model.…”

“…21 Most importantly, several reports have shown that SAP strongly binds to CD14 + monocytes 22 and opsonizes its ligands in an Fc receptor-dependent manner. [23][24][25][26] In this regard, hSAP has been considered a candidate DNA vaccine 'scavenger' that requires further investigation. In this study, we investigated the plasmid-binding and the DNA clearance activities of hSAP and the role of SAP in plasmid transfection in vitro and in vivo.…”