Radiation-induced lung injury and inflammation in mice: Role of inducible nitric oxide synthase and surfactant protein D

Rama Malaviya, Andrew J. Gow, Mary Francis, Elena V. Abramova, Jeffrey D. Laskin, Debra L. Laskin

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27 Citations (Scopus)

Abstract

Reactive nitrogen species (RNS) generated after exposure to radiation have been implicated in lung injury. Surfactant protein D (SP-D) is a pulmonary collectin that suppresses inducible nitric oxide synthase (iNOS)-mediated RNS production. Herein, we analyzed the role of iNOS and SP-D in radiation-induced lung injury. Exposure of wild-type (WT) mice to γ-radiation (8 Gy) caused acute lung injury and inflammation, as measured by increases in bronchoalveolar lavage (BAL) protein and cell content at 24 h. Radiation also caused alterations in SP-D structure at 24h and 4 weeks post exposure. These responses were blunted in iNOS-/- mice. Conversely, loss of iNOS had no effect on radiation-induced expression of phospho-H2A.X or tumor necrosis factor (TNF)-α. Additionally, at 24h post radiation, cyclooxygenase expression and BAL lipocalin-2 levels were increased in iNOS-/- mice, and heme oxygenase (HO)-1+ and Ym1+ macrophages were evident. Loss of SP-D resulted in increased numbers of enlarged HO-1+ macrophages in the lung following radiation, along with upregulation of TNF-α, CCL2, and CXCL2, whereas expression of phospho-H2A.X was diminished. To determine if RNS play a role in the altered sensitivity of SP-D-/- mice to radiation, iNOS-/-/SP-D-/- mice were used. Radiation-induced injury, oxidative stress, and tissue repair were generally similar in iNOS-/-/SP-D-/- and SP-D-/- mice. In contrast, TNF-α, CCL2, and CXCL2 expression was attenuated. These data indicate that although iNOS is involved in radiation-induced injury and altered SP-D structure, in the absence of SP-D, it functions to promote proinflammatory signaling. Thus, multiple inflammatory pathways contribute to the pathogenic response to radiation.

Original languageEnglish
Pages (from-to)27-38
Number of pages12
JournalToxicological Sciences
Volume144
Issue number1
DOIs
Publication statusPublished - 1 Mar 2015
Externally publishedYes

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Keywords

  • iNOS
  • Lung injury
  • Radiation
  • Reactive nitrogen species
  • Surfactant protein D

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

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