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

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.

• Authors: Hisatsugu Goto, Julie G Ledford, Sambuddho Mukherjee, Paul W Noble, Kristi L Williams, Jo Rae Wright
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 181 Issue 12 Pg. 1336-44 (Jun 15 2010) ISSN: 1535-4970 [Electronic] United States
• PMID: 20167853 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• Pulmonary Surfactant-Associated Protein A
• Bleomycin

Topics

• Acute Lung Injury (chemically induced, metabolism)
• Animals
• Apoptosis (drug effects)
• Bleomycin
• Bronchoalveolar Lavage Fluid
• Cell Culture Techniques (methods)
• Cytokines (drug effects, metabolism)
• Disease Models, Animal
• Edema
• Enzyme-Linked Immunosorbent Assay (methods)
• Epithelial Cells (drug effects, metabolism)
• Female
• In Situ Nick-End Labeling (methods)
• Inflammation (metabolism)
• Lung (drug effects, metabolism)
• Mice
• Mice, Inbred C57BL
• Pulmonary Surfactant-Associated Protein A (metabolism)