Serum amyloid P component and C-reactive protein mediate phagocytosis through murine Fc gamma Rs.
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 FcgammaR. Mice deficient in FcgammaR 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 FcgammaR 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 FcgammaRII. SAP and CRP opsonized zymosan for phagocytosis by BMM from mice deficient in FcgammaRII or FcgammaRIII. SAP, but not CRP, opsonized zymosan for uptake by neutrophils that express only low levels of FcgammaRI. Together these results indicate that FcgammaRI and FcgammaRIII are receptors for SAP in the mouse. Opsonization of zymosan by CRP is mediated through FcgammaRI. Pentraxins are major proteins of the innate immune system and arose earlier in evolution than Igs. The use of FcgammaR 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.
Mold
C
C
Department of Molecular Genetics and Microbiology, Veterans Affairs Medical Center, and Department of Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
Gresham
H D
HD
Du Clos
T W
TW
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007142:Immunoglobulin gamma-Chains / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D017452:Receptors, IgG / Q000502:physiology*; D000683:Serum Amyloid P-Component / Q000378:metabolism / Q000502:physiology*; D015054:Zymosan / Q000378:metabolism
D000276:Adjuvants, Immunologic; D007142:Immunoglobulin gamma-Chains; D009895:Opsonin Proteins; D017452:Receptors, IgG; D000683:Serum Amyloid P-Component; D002097:C-Reactive Protein; D015054:Zymosan