| First Author | Malaviya R | Year | 2015 |
| Journal | Toxicol Sci | Volume | 144 |
| Issue | 1 | Pages | 27-38 |
| PubMed ID | 25552309 | Mgi Jnum | J:227785 |
| Mgi Id | MGI:5702805 | Doi | 10.1093/toxsci/kfu255 |
| Citation | Malaviya R, et al. (2015) Radiation-induced lung injury and inflammation in mice: role of inducible nitric oxide synthase and surfactant protein D. Toxicol Sci 144(1):27-38 |
| abstractText | 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 gamma-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 24 h 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)-alpha. Additionally, at 24 h 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-alpha, 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-alpha, 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. |
