Surfactant protein D protects against acute hyperoxic lung injury

Deepika Jain, Elena N. Atochina-Vasserman, Yaniv Tomer, Helchem Kadire, Michael F. Beers

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Rationale: Surfactant protein D (SP-D) is a member of the collectin family of soluble, innate, host defense molecules with demonstrated immunomodulatory properties in vitro. Constitutive absence of SP-D in mice is associated with lung inflammation, alteration in surfactant lipid homeostasis, and increased oxidative-nitrative stress. Objectives: To test the hypothesis that SP-D would protect against acute lung injury from hyperoxia in vivo. Methods: Transgenic mice overexpressing rat SP-D-constitutively (SPDOE) or conditionally via regulation with doxycycline (SP-D Dox-on) were subjected to continuous hyperoxic challenge for up to 14 days. Measurements and Main Results: Compared with littermate control mice (wild-type [WT]), SP-D OE mice exposed to 80% O 2 demonstrated substantially increased survival accompanied by significant reductions in wet to dry lung ratios and bronchoalveolar lavage (BAL) protein. Although SP-DOE and WT mice exhibited a twofold increase in total BAL cells and neutrophilia in response to hyperoxia, the SP-D OE group had lower levels of BAL proinflammatory cytokines and chemokines, including IL-6, tumor necrosis factor-α, and monocyte chemotactic protein-1; increased mRNA levels of the transcription factor NF-E2 related factor-2 (NRF-2) and phase 2 antioxidants hemoxygenase-1 (HO-1), glutathione peroxidase-2 (GPx-2) and NAD(P)H quinone oxidoreductase-1 (Nqo-1); and decreases in lung tissue thiobarbituric acid-reactive substances. As proof of principle, the protective role of SP-Don hyperoxic injurywas confirmed as SP-D Dox-on mice exposed to 85% O2 demonstrated increased mortality upon withdrawal of doxycycline. Conclusions: Local expression of SP-D protects against hyperoxic lung injury through modulation of proinflammatory cytokines and antioxidant enzymatic scavenger systems.

Original languageEnglish
Pages (from-to)805-813
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume178
Issue number8
DOIs
Publication statusPublished - 15 Oct 2008
Externally publishedYes

Keywords

  • Antioxidants
  • Collectin
  • Inflammation
  • Innate immunity
  • Oxidative stress

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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