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

LA Murray, R Rosada, AP Moreira, A Joshi, MS Kramer… - PloS one, 2010 - journals.plos.org
LA Murray, R Rosada, AP Moreira, A Joshi, MS Kramer, DP Hesson, RL Argentieri, S Mathai…
PloS one, 2010journals.plos.org
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 …
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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