SP-D-deficient mice are resistant to hyperoxia

Deepika Jain, Elena Atochina-Vasserman, Helchem Kadire, Yaniv Tomer, Adam Inch, Pamela Scott, Rashmin C. Savani, Andrew J. Gow, Michael F. Beers

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19 Citations (Scopus)

Abstract

Surfactant protein D (SP-D), a member of the collectin superfamily, modulates pulmonary inflammatory responses and innate immunity. Disruption of the SP-D gene in mice induces peribronchiolar inflammation, accumulation of large, foamy macrophages, increased bronchoalveolar lavage (BAL) phospholipid, and pulmonary emphysema. We hypothesized that absence of SP-D aggravates hyperoxia-induced injury. To test this, SP-D-deficient (SP-D-/-) and wild-type (SP-D+/+) mice were exposed to 80% or 21% oxygen. Paradoxically, during 14 days of hyperoxia, SP-D-/- mice had 100% survival vs. 30% in SP-D+/+. The survival advantage in SP-D -/- mice was accompanied by lower histopathological injury scores at days 5 and 14, although total BAL cells (8.2 ± 1.4 × 105 in SP-D-/- vs. 4.04 ± 0.25 ± 105 in SP-D-/- mice) and neutrophils (1.2 ± 0.4 × 10 5 vs. 0.03 ± 0.02 × 105 in SP-D-/- and SP-D+/+, respectively) were increased. In addition, BAL protein and lung-to-body weight ratios were similarly elevated in both groups after 3, 5, and 14 days of continuous exposure. Biochemically, in contrast to SP-D +/+, SP-D-/- mice had higher levels of surfactant phospholipid and SP-B at baseline and 5 days after hyperoxia accompanied by a preservation of surfactant biophysical activity. From a multiplex assay of nine cytokines, we found elevated levels of IL-13 in BAL fluid of normoxic SP-D -/- mice compared with SP-D+/+. We conclude that the resistance of SP-D-deficient mice to hyperoxia reflects homeostatic changes in the SP-D-/- phenotype involving both phospholipid and SP-B-mediated induced resistance of surfactant to inactivation as well as changes in the immunomodulatory BAL cytokine profile.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume292
Issue number4
DOIs
Publication statusPublished - Apr 2007
Externally publishedYes

Keywords

  • Alveolar macrophages
  • Collectin
  • Inflammation
  • Surfactant protein D

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

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  • Cite this

    Jain, D., Atochina-Vasserman, E., Kadire, H., Tomer, Y., Inch, A., Scott, P., Savani, R. C., Gow, A. J., & Beers, M. F. (2007). SP-D-deficient mice are resistant to hyperoxia. American Journal of Physiology - Lung Cellular and Molecular Physiology, 292(4). https://doi.org/10.1152/ajplung.00145.2006