Serum Amyloid P Therapeutically Attenuates Murine Bleomycin-Induced Pulmonary Fibrosis via Its Effects on Macrophages |
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| Authors: | Lynne A Murray Rogerio Rosada Ana Paula Moreira Amrita Joshi Michael S Kramer David P Hesson Rochelle L Argentieri Susan Mathai Mridu Gulati Erica L Herzog Cory M Hogaboam |
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| Institution: | 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.;University of Pittsburgh, United States of America |
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| 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 Fcγ 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 may extend to many fibrotic indications caused by over-exuberant pro-fibrotic macrophage responses. |
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