The role of alveolar epithelium in radiation-induced lung injury

• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053628

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.