Alveolar surfactant protein D content modulates bleomycin-induced lung injury

John Casey, Jennifer Kaplan, Elena N. Atochina-Vasserman, Andrew J. Gow, Helchem Kadire, Yaniv Tomer, James H. Fisher, Samuel Hawgood, Rashmin C. Savani, Michael F. Beers

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    45 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)869-877
    Number of pages9
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume172
    Issue number7
    DOIs
    Publication statusPublished - 1 Oct 2005

    Keywords

    • Bleomycin
    • Collectins
    • Innate immunity
    • Lung
    • Nitric oxide

    ASJC Scopus subject areas

    • Pulmonary and Respiratory Medicine

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  • Cite this

    Casey, J., Kaplan, J., Atochina-Vasserman, E. N., Gow, A. J., Kadire, H., Tomer, Y., Fisher, J. H., Hawgood, S., Savani, R. C., & Beers, M. F. (2005). Alveolar surfactant protein D content modulates bleomycin-induced lung injury. American Journal of Respiratory and Critical Care Medicine, 172(7), 869-877. https://doi.org/10.1164/rccm.200505-767OC