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 language | English |
|---|---|
| Pages (from-to) | 27-38 |
| Number of pages | 12 |
| Journal | Toxicological Sciences |
| Volume | 144 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Mar 2015 |
| Externally published | Yes |
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Keywords
- iNOS
- Lung injury
- Radiation
- Reactive nitrogen species
- Surfactant protein D
ASJC Scopus subject areas
- Toxicology
- Medicine(all)
Cite this
Radiation-induced lung injury and inflammation in mice : Role of inducible nitric oxide synthase and surfactant protein D. / Malaviya, Rama; Gow, Andrew J.; Francis, Mary; Abramova, Elena V.; Laskin, Jeffrey D.; Laskin, Debra L.
In: Toxicological Sciences, Vol. 144, No. 1, 01.03.2015, p. 27-38.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Radiation-induced lung injury and inflammation in mice
T2 - Role of inducible nitric oxide synthase and surfactant protein D
AU - Malaviya, Rama
AU - Gow, Andrew J.
AU - Francis, Mary
AU - Abramova, Elena V.
AU - Laskin, Jeffrey D.
AU - Laskin, Debra L.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - iNOS
KW - Lung injury
KW - Radiation
KW - Reactive nitrogen species
KW - Surfactant protein D
UR - http://www.scopus.com/inward/record.url?scp=84924440252&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924440252&partnerID=8YFLogxK
U2 - 10.1093/toxsci/kfu255
DO - 10.1093/toxsci/kfu255
M3 - Article
C2 - 25552309
AN - SCOPUS:84924440252
VL - 144
SP - 27
EP - 38
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 1
ER -