Published ahead of print on June 30, 2005, doi:10.1164/rccm.200505-767OC
© 2005 American Thoracic Society doi: 10.1164/rccm.200505-767OC
Alveolar Surfactant Protein D Content Modulates Bleomycin-induced Lung InjuryDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania School of Medicine; Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Division of Pulmonary Sciences and Critical Care Medicine, Denver Health Medical Center, Denver, Colorado ; and Department of Pediatrics and Division of Neonatology, University of California at San Francisco, San Francisco, California Correspondence and requests for reprints should be addressed to Michael F. Beers, M.D., Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, 807 BRB II/III Building, 421 Curie Boulevard, Philadelphia, PA 19104. E-mail: mfbeers{at}mail.med.upenn.edu Rationale: Surfactant protein D (SP-D) is a collectin family member with demonstrated immunomodulatory properties in vitro. We hypothesized that SP-D modulates inflammation during noninfectious lung injury in vivo. Objectives: To investigate the association of alveolar SP-D and injury, we studied the responses of transgenic mice expressing varying levels of SP-D to intratracheal bleomycin (ITB). Methods: Eight-week old C57/BL6 SP-D–deficient (–/–) mice and syngeneic wild-type (WT) controls or Swiss Black SP-D–overexpressing (SP-D OE) mice and littermate controls received either ITB or saline and were followed for up to 21 d. Measurements and Results: Kaplan-Meier analysis demonstrated a dose-dependent decrease in survival in ITB SP-D (–/–) mice receiving 2 U/kg bleomycin, with a 14-d mortality of 100% versus 0% mortality for WT receiving 2 U/kg ITB or SP-D (–/–) mice given saline (p < 0.05). At 8 d, ITB SP-D (–/–) mice had greater respiratory distress (frequency/tidal volume) and weight loss than ITB WT mice. Furthermore, bronchoalveolar lavage cellularity, pulmonary parenchymal inflammation, and tissue 3-nitrotyrosine (NO2 Y) were increased to a greater extent in ITB SP-D (–/–) mice. By 21 d, compared with all groups, ITB SP-D (–/–) survivors had increased Trichrome staining and tissue hydroxyproline levels. As proof of principle, SP-D OE mice were highly resistant to bleomycin-induced morbidity and mortality at doses up to 3 U/kg. Conclusions: These data provide new in vivo evidence for an antiinflammatory role for SP-D in response to noninfectious, subacute lung injury via modulation of oxidative-nitrative stress.
Key Words: bleomycin • collectins • innate immunity • lung • nitric oxide This article has been cited by other articles:
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