title: Distinct Fcγ receptors mediate the effect of serum amyloid p on neutrophil adhesion and fibrocyte differentiation.
abstract: The plasma protein serum amyloid P (SAP) reduces neutrophil adhesion, inhibits the differentiation of monocytes into fibroblast-like cells called fibrocytes, and promotes phagocytosis of cell debris by macrophages. Together, these effects of SAP reduce key aspects of inflammation and fibrosis, and SAP injections improve lung function in pulmonary fibrosis patients. SAP functions are mediated, in part, by FcγRs, but the contribution of each FcγR is not fully understood. We found that aa Q55 and E126 in human SAP affect human fibrocyte differentiation and SAP binding to FcγRI. E126, K130, and Q128 affect neutrophil adhesion and SAP affinity for FcγRIIa. Q128 also affects phagocytosis by macrophages and SAP affinity for FcγRI. All the identified functionally significant amino acids in SAP form a binding site that is distinct from the previously described SAP-FcγRIIa binding site. Blocking FcγRI with an IgG-blocking Ab reduces the SAP effect on fibrocyte differentiation, and ligating FcγRIIa with Abs reduces neutrophil adhesion. Together, these results suggest that SAP binds to FcγRI on monocytes to inhibit fibrocyte differentiation, and binds to FcγRIIa on neutrophils to reduce neutrophil adhesion.
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843.
authors.forename: Nehemiah
authors.initials: N
authors.lastname: Cox
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843.
authors.forename: Darrell
authors.initials: D
authors.lastname: Pilling
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843 rgomer@tamu.edu.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gomer
mesh_terms: D000595:Amino Acid Sequence; D019138:Antibodies, Blocking / Q000276:immunology; D001666:Binding Sites, Antibody; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology; D005355:Fibrosis / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D020033:Protein Isoforms / Q000235:genetics; D017452:Receptors, IgG / Q000276:immunology*; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; C489017:FCGR1A protein, human; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D020033:Protein Isoforms; D017452:Receptors, IgG; D000683:Serum Amyloid P-Component