Hisatsugu Goto1, Julie G. Ledford1, Sambuddho Mukherjee1, Paul W. Noble2, Kristi L. Williams1,3 and Jo Rae Wright1. Published ahead of print on February 18, 2010. American Journal of Respiratory and Critical Care Medicine Vol 181. pp. 1336-1344, (2010)
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.
Weblink here
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.
Weblink here