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

Research output: Contribution to journalArticle

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

Fingerprint

Pulmonary Surfactant-Associated Protein D
Hyperoxia
Bronchoalveolar Lavage
Surface-Active Agents
Phospholipids
Collectins
Cytokines

Keywords

  • Alveolar macrophages
  • Collectin
  • Inflammation
  • Surfactant protein D

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

SP-D-deficient mice are resistant to hyperoxia. / Jain, Deepika; Atochina-Vasserman, Elena; Kadire, Helchem; Tomer, Yaniv; Inch, Adam; Scott, Pamela; Savani, Rashmin C.; Gow, Andrew J.; Beers, Michael F.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 292, No. 4, 04.2007.

Research output: Contribution to journalArticle

Jain, Deepika ; Atochina-Vasserman, Elena ; Kadire, Helchem ; Tomer, Yaniv ; Inch, Adam ; Scott, Pamela ; Savani, Rashmin C. ; Gow, Andrew J. ; Beers, Michael F. / SP-D-deficient mice are resistant to hyperoxia. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2007 ; Vol. 292, No. 4.
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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.",
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AU - Jain, Deepika

AU - Atochina-Vasserman, Elena

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AU - Inch, Adam

AU - Scott, Pamela

AU - Savani, Rashmin C.

AU - Gow, Andrew J.

AU - Beers, Michael F.

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AB - 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.

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