| First Author | Crawford JR | Year | 2012 |
| Journal | J Leukoc Biol | Volume | 92 |
| Issue | 4 | Pages | 699-711 |
| PubMed ID | 22493081 | Mgi Jnum | J:189442 |
| Mgi Id | MGI:5445821 | Doi | 10.1189/jlb.0112033 |
| Citation | Crawford JR, et al. (2012) FcgammaRI mediates serum amyloid P inhibition of fibrocyte differentiation. J Leukoc Biol 92(4):699-711 |
| abstractText | 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 (FcgammaR) and has been crystallized bound to FcgammaRIIa (CD32a). The in vivo activity of SAP appears to be dependent on the FcRgamma. We find that mutagenesis of the residues critical for SAP binding to FcgammaRIIa only moderately decreases the ability of SAP to inhibit fibrocyte differentiation. In murine cells, deletion of FcRgamma or FcgammaRI (CD64) significantly reduced sensitivity to SAP. Deletion of the combination of FcgammaRIIb, FcgammaRIIIa, and FcgammaRIV did not significantly affect sensitivity to SAP, whereas deletion of just the inhibitory receptor FcgammaRIIb (CD32b) increased sensitivity to SAP. In human cells, siRNA-mediated reduction of FcRgamma or FcgammaRI levels significantly decreased sensitivity to SAP, whereas reduction of FcgammaRIIb levels increased sensitivity to SAP. These observations suggest that SAP, at least in part, uses FcgammaRI and FcRgamma to inhibit fibrocyte differentiation. |
