The role of alveolar epithelium in radiation-induced lung injury

Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11-13...

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Bibliographic Details
Published in:	PloS one Vol. 8; no. 1; p. e53628
Main Authors:	Almeida, Celine, Nagarajan, Devipriya, Tian, Jian, Leal, Sofia Walder, Wheeler, Kenneth, Munley, Michael, Blackstock, William, Zhao, Weiling
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 11-01-2013 Public Library of Science (PLoS)
Subjects:	Actin Alveoli Analysis Animals Aquaporin 5 - metabolism Biology Brain cancer Cadherins - metabolism Cell Line Cesium isotopes Cesium radioisotopes Chromatin Collagen Complications Complications and side effects Dose Fractionation Dose-Response Relationship, Radiation Drug dosages E-cadherin Edema Epithelium Epithelium - pathology Epithelium - radiation effects Female Fibroblasts Fibrosis Gamma Rays Hepatology Immunofluorescence Inflammation Intermediate filament proteins Irradiation Laboratories Localization Lung cancer Lung Injury - complications Lung Injury - pathology Lungs Medicine Mesenchyme Mice Mice, Inbred Strains Morbidity Muscle proteins Muscles Oncology Oxidative stress Pneumonia Pneumonitis Protein C Protein Transport - radiation effects Pulmonary Alveoli - metabolism Pulmonary Alveoli - pathology Pulmonary Alveoli - radiation effects Pulmonary fibrosis Pulmonary Surfactant-Associated Protein C - metabolism Radiation Radiation (Physics) Radiation effects Radiation injuries Radiation Injuries - complications Radiation Injuries - pathology Radiation therapy Rodents Smooth muscle Survival Analysis Thickening Thorax Time Factors Transforming Growth Factor beta1 - metabolism Vascular Cell Adhesion Molecule-1 - metabolism Vimentin Vimentin - metabolism North Carolina United States > US
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Summary:	Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11-13 Gy) and fractionated doses (24-36 Gy) of (137)Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c(+) cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis.
Bibliography:	Conceived and designed the experiments: WZ KW WB MM. Performed the experiments: CA DN WZ. Analyzed the data: STS JT WZ. Contributed reagents/materials/analysis tools: WZ. Wrote the paper: WZ. Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0053628