serum amyloid p therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages血清淀粉样蛋白p治疗减弱小鼠bleomycin-induced肺纤维化通过其对巨噬细胞的影响.pdfVIP

Serum Amyloid P Therapeutically Attenuates Murine Bleomycin-Induced Pulmonary Fibrosis via Its Effects on Macrophages 1 2 2 2 1 Lynne A. Murray *, Rogerio Rosada , Ana Paula Moreira , Amrita Joshi , Michael S. Kramer , David P. 1 1 3 3 3 2 Hesson , Rochelle L. Argentieri , Susan Mathai , Mridu Gulati , Erica L. Herzog , Cory M. Hogaboam 1 Promedior, Inc., Malvern, Pennsylvania, United States of America, 2 Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America, 3 Internal Medicine, Pulmonary and Critical Care Division, Yale University School of Medicine, New Haven, Connecticut, United States of America Abstract Macrophages promote tissue remodeling but few mechanisms exist to modulate their activity during tissue fibrosis. Serum amyloid P (SAP), a member of the pentraxin family of proteins, signals through Fcc receptors which are known to affect macrophage activation. We determined that IPF/UIP patients have increased protein levels of several alternatively activated pro-fibrotic (M2) macrophage-associated proteins in the lung and monocytes from these patients show skewing towards an M2 macrophage phenotype. SAP therapeutically inhibits established bleomycin-induced pulmonary fibrosis, when administered systemically or locally to the lungs. The reduction in aberrant collagen deposition was associated with a reduction in M2 macrophages in the lung and increased IP10/CXCL10. These data highlight the role of macrophages in fibrotic lung disease, and demonstrate a therapeutic action of SAP on macrophages which