Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages

PLoS One. 2010 Mar 12;5(3):e9683. doi: 10.1371/journal.pone.0009683.


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 Fcgamma 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Bleomycin / pharmacology*
  • Collagen / metabolism
  • Female
  • Fibrosis
  • Humans
  • Lung / pathology
  • Lung Diseases / pathology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Male
  • Mice
  • Middle Aged
  • Pulmonary Fibrosis / chemically induced*
  • Serum Amyloid P-Component / biosynthesis*


  • Serum Amyloid P-Component
  • Bleomycin
  • Collagen