Distinct Fc receptors mediate the effect of serum amyloid p on neutrophil adhesion and fibrocyte differentiation.
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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 FcRs, but the contribution of each FcR is not fully understood. We found that aa Q55 and E126 in human SAP affect human fibrocyte differentiation and SAP binding to FcRI. E126, K130, and Q128 affect neutrophil adhesion and SAP affinity for FcRIIa. Q128 also affects phagocytosis by macrophages and SAP affinity for FcRI. All the identified functionally significant amino acids in SAP form a binding site that is distinct from the previously described SAP-FcRIIa binding site. Blocking FcRI with an IgG-blocking Ab reduces the SAP effect on fibrocyte differentiation, and ligating FcRIIa with Abs reduces neutrophil adhesion. Together, these results suggest that SAP binds to FcRI on monocytes to inhibit fibrocyte differentiation, and binds to FcRIIa on neutrophils to reduce neutrophil adhesion.
