title: Surfactant protein-D regulates effector cell function and fibrotic lung remodeling in response to bleomycin injury.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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-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.
  
  
  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 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.
  
  
  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.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aono
authors.forename: Julie G
authors.initials: JG
authors.lastname: Ledford
authors.forename: Sambuddho
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Ogawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nishioka
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
authors.forename: Michael F
authors.initials: MF
authors.lastname: Beers
authors.forename: Paul W
authors.initials: PW
authors.lastname: Noble
authors.forename: Jo Rae
authors.initials: JR
authors.lastname: Wright
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000503:physiopathology; D056151:Airway Remodeling / Q000502:physiology; D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D037662:Pulmonary Surfactant-Associated Protein A / Q000032:analysis / Q000502:physiology; D037663:Pulmonary Surfactant-Associated Protein D / Q000032:analysis / Q000502:physiology*; D051381:Rats
chemical_list: D016207:Cytokines; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D001761:Bleomycin