Surfactant protein-D regulates effector cell function and fibrotic lung remodeling in response to bleomycin injury.

Published

Journal Article

Surfactant protein (SP)-D and SP-A have been implicated in immunomodulation in the lung. It has been reported that patients with idiopathic pulmonary fibrosis (IPF) often have elevated serum levels of SP-A and SP-D, although their role in the disease is not known.The goal of this study was to test the hypothesis that SP-D plays an important role in lung fibrosis using a mouse model of fibrosis induced by bleomycin (BLM).Triple transgenic inducible SP-D mice (iSP-D mice), in which rat SP-D is expressed in response to doxycycline (Dox) treatment, were administered BLM (100 U/kg) or saline subcutaneously using miniosmotic pumps.BLM-treated iSP-D mice off Dox (SP-D off) had increased lung fibrosis compared with mice on Dox (SP-D on). SP-D deficiency also increased macrophage-dominant cell infiltration and the expression of profibrotic cytokines (transforming growth factor [TGF]-β1, platelet-derived growth factor-AA). Alveolar macrophages isolated from BLM-treated iSP-D mice off Dox (SP-D off) secreted more TGF-β1. Fibrocytes, which are bone marrow-derived mesenchymal progenitor cells, were increased to a greater extent in the lungs of the BLM-treated iSP-D mice off Dox (SP-D off). Fibrocytes isolated from BLM-treated iSP-D mice off Dox (SP-D off) expressed more of the profibrotic cytokine TGF-β1 and more CXCR4, a chemokine receptor that is important in fibrocyte migration into the lungs. Exogenous SP-D administered intratracheally attenuated BLM-induced lung fibrosis in SP-D(-/-) mice.These data suggest that alveolar SP-D regulates numbers of macrophages and fibrocytes in the lungs, profibrotic cytokine expression, and fibrotic lung remodeling in response to BLM injury.

Full Text

Cited Authors

  • Aono, Y; Ledford, JG; Mukherjee, S; Ogawa, H; Nishioka, Y; Sone, S; Beers, MF; Noble, PW; Wright, JR

Published Date

  • March 2012

Published In

Volume / Issue

  • 185 / 5

Start / End Page

  • 525 - 536

PubMed ID

  • 22198976

Pubmed Central ID

  • 22198976

Electronic International Standard Serial Number (EISSN)

  • 1535-4970

International Standard Serial Number (ISSN)

  • 1073-449X

Digital Object Identifier (DOI)

  • 10.1164/rccm.201103-0561OC

Language

  • eng