The role of surfactant protein A in bleomycin-induced acute lung injury

Hisatsugu Goto, Julie G. Ledford, Sambuddho Mukherjee, Paul W. Noble, Kristi L. Williams, Jo Rae Wright

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Rationale: 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. Objectives: 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. Measurements and Main 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.

Original languageEnglish (US)
Pages (from-to)1336-1344
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume181
Issue number12
DOIs
StatePublished - Jun 15 2010
Externally publishedYes

Keywords

  • Apoptosis
  • Collectin
  • Noninfectious lung injury
  • Surfactant replacement therapy

ASJC Scopus subject areas

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

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