title: The role of surfactant protein A in bleomycin-induced acute lung injury.
abstract: BACKGROUND
  Surfactant protein A (SP-A) is a collectin family member that has multiple immunomodulatory roles in lung host defense. SP-A levels are altered in the bronchoalveolar lavage (BAL) fluid and serum of patients with acute lung injury and acute respiratory distress syndrome, suggesting the importance of SP-A in the pathogenesis of acute lung injury.
  
  
  OBJECTIVE
  Investigate the role of SP-A in the murine model of noninfectious lung injury induced by bleomycin treatment.
  
  
  METHODS
  Wild-type (WT) or SP-A deficient (SP-A(-/-)) mice were challenged with bleomycin, and various indices of lung injury were analyzed.
  
  
  RESULTS
  On challenge with bleomycin, SP-A(-/-) mice had a decreased survival rate as compared with WT mice. SP-A(-/-) mice had a higher degree of neutrophil-dominant cell recruitment and the expression of the inflammatory cytokines in BAL fluid than did WT mice. In addition, SP-A(-/-) mice had increased lung edema as assessed by the increased levels of intravenously injected Evans blue dye leaking into the lungs. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and active caspase-3 staining suggested the increased apoptosis in the lung sections from SP-A(-/-) mice challenged with bleomycin. SP-A also specifically reduced bleomycin-induced apoptosis in mouse lung epithelial 12 cells in vitro. Moreover, intratracheal administration of exogenous SP-A rescued the phenotype of SP-A(-/-) mice in vivo.
  
  
  CONCLUSIONS
  These data suggest that SP-A plays important roles in modulating inflammation, apoptosis, and epithelial integrity in the lung in response to acute noninfectious challenges.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA.
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Goto
authors.forename: Julie G
authors.initials: JG
authors.lastname: Ledford
authors.forename: Sambuddho
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Paul W
authors.initials: PW
authors.lastname: Noble
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Williams
authors.forename: Jo Rae
authors.initials: JR
authors.lastname: Wright
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid; D018929:Cell Culture Techniques / Q000379:methods; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020287:In Situ Nick-End Labeling / Q000379:methods; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism*
chemical_list: D016207:Cytokines; D037662:Pulmonary Surfactant-Associated Protein A; D001761:Bleomycin