The role of surfactant protein A in bleomycin-induced acute lung injury.
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.
Goto
Hisatsugu
H
Department of Cell Biology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA.
Ledford
Julie G
JG
Mukherjee
Sambuddho
S
Noble
Paul W
PW
Williams
Kristi L
KL
Wright
Jo Rae
JR
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*
D016207:Cytokines; D037662:Pulmonary Surfactant-Associated Protein A; D001761:Bleomycin