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

Yoshinori Aono, Julie G. Ledford, Sambuddho Mukherjee, Hirohisa Ogawa, Yasuhiko Nishioka, Saburo Sone, Michael F. Beers, Paul W. Noble, Jo Rae W. Wright

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Rationale: Surfactant protein (SP)-D and SP-A have been implicated inimmunomodulation 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. Objectives: 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). Methods: Triple transgenic inducible SP-Dmice(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. Measurements and Main Results: 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 infiltrationandthe 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 moreof 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)525-536
Number of pages12
JournalAmerican journal of respiratory and critical care medicine
Volume185
Issue number5
DOIs
StatePublished - Mar 1 2012

Keywords

  • Fibrocyte
  • Growth factor
  • Lung fibrosis
  • Macrophage
  • Surfactant

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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