FcRI mediates serum amyloid P inhibition of fibrocyte differentiation. Academic Article uri icon


  • Fibrotic diseases, such as cardiac and pulmonary fibrosis, have a poor prognosis with no FDA approved therapies. Monocyte-derived, fibroblast-like cells, called fibrocytes, participate in the formation of fibrotic lesions. The conserved pentraxin protein SAP inhibits fibrocyte differentiation in cell culture, and injections of SAP significantly reduce fibrosis in several animal models. SAP binds to the receptors for the Fc portion of IgG (FcR) and has been crystallized bound to FcRIIa (CD32a). The in vivo activity of SAP appears to be dependent on the FcR. We find that mutagenesis of the residues critical for SAP binding to FcRIIa only moderately decreases the ability of SAP to inhibit fibrocyte differentiation. In murine cells, deletion of FcR or FcRI (CD64) significantly reduced sensitivity to SAP. Deletion of the combination of FcRIIb, FcRIIIa, and FcRIV did not significantly affect sensitivity to SAP, whereas deletion of just the inhibitory receptor FcRIIb (CD32b) increased sensitivity to SAP. In human cells, siRNA-mediated reduction of FcR or FcRI levels significantly decreased sensitivity to SAP, whereas reduction of FcRIIb levels increased sensitivity to SAP. These observations suggest that SAP, at least in part, uses FcRI and FcR to inhibit fibrocyte differentiation.

published proceedings

  • J Leukoc Biol

altmetric score

  • 3

author list (cited authors)

  • Crawford, J. R., Pilling, D., & Gomer, R. H.

citation count

  • 47

complete list of authors

  • Crawford, Jeffrey R||Pilling, Darrell||Gomer, Richard H

publication date

  • January 2012