Serum amyloid P component and C-reactive protein mediate phagocytosis through murine FcγRs

The pentraxins, serum amyloid P component (SAP) and C-reactive protein (CRP) are acute-phase serum proteins in mice and humans, respectively. Although SAP binds to DNA and chromatin and affects clearance of these autoantigens, no specific receptor for SAP has been identified. CRP is an opsonin, and we have shown that it binds to Fc gammaR. Mice deficient in Fc gammaR were used to assess the role of these receptors in phagocytosis by pentraxins using zymosan as a ligand. Phagocytosis of zymosan by bone marrow macrophages (BMM) was enhanced by opsonization with SAP or CRP. BMM from mice deficient in all three Fc gammaR or in gamma -chain ingested unopsonized zymosan, but phagocytosis of SAP- or CRP-opsonized zymosan was not enhanced. SAP binding to BMM from gamma -chain-deficient mice was also greatly reduced, indicating little or no binding of SAP to Fc gamma RII, SAP and CRP opsonized zymosan for phagocytosis by BMM from mice deficient in Fc gamma RII or Fc gamma RIII, SAP, but nut CRP, opsonized zymosan for uptake by neutrophils that express only low levels of Fc gamma RI. Together these results indicate that Fc gamma RI and Fc gamma RIII are receptors for SAP in the mouse. Opsonization of zymosan by CRP is mediated through Fc gamma RI. Pentraxins are major proteins of the innate immune system and arose earlier in evolution than Igs. The use of Fc gammaR by the pentraxins links innate and adaptive immunity and may have important consequences for processing, presentation, and clearance of the self-Ags to which these proteins bind.