title: Radiation-induced impairment in lung lymphatic vasculature.
abstract: BACKGROUND
  The lymphatic vasculature has been shown to play important roles in lung injury and repair, particularly in lung fibrosis. The effects of ionizing radiation on lung lymphatic vasculature have not been previously reported.
  
  
  RESULTS
  C57Bl/6 mice were immobilized in a lead shield exposing only the thoracic cavity, and were irradiated with a single dose of 14 Gy. Animals were sacrificed and lungs collected at different time points (1, 4, 8, and 16 weeks) following radiation. To identify lymphatic vessels in lung tissue sections, we used antibodies that are specific for lymphatic vessel endothelial receptor 1 (LYVE-1), a marker of lymphatic endothelial cells (LEC). To evaluate LEC cell death and oxidative damage, lung tissue sections were stained for LYVE-1 and with TUNEL staining, or 8-oxo-dG respectively. Images were imported into ImageJ v1.36b and analyzed. Compared to a non-irradiated control group, we observed a durable and progressive decrease in the density, perimeter, and area of lymphatic vessels over the study period. The decline in the density of lymphatic vessels was observed in both subpleural and interstitial lymphatics. Histopathologically discernible pulmonary fibrosis was not apparent until 16 weeks after irradiation. Furthermore, there was significantly increased LEC apoptosis and oxidative damage at one week post-irradiation that persisted at 16 weeks.
  
  
  CONCLUSIONS
  There is impairment of lymphatic vasculature after a single dose of ionizing radiation that precedes architectural distortion and fibrosis, suggesting important roles for the lymphatic circulation in the pathogenesis of the radiation-induced lung injury.
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Ye
authors.initials: Y
authors.lastname: Cui
authors.forename: Julie
authors.initials: J
authors.lastname: Wilder
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rietz
authors.forename: Andrew
authors.initials: A
authors.lastname: Gigliotti
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Tang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shi
authors.forename: Raymond
authors.initials: R
authors.lastname: Guilmette
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Gautam
authors.initials: G
authors.lastname: George
authors.forename: Eduarda
authors.initials: E
authors.lastname: Nilo de Magaldi
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Chu
authors.forename: Melanie
authors.initials: M
authors.lastname: Doyle-Eisele
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
authors.forename: Ivan O
authors.initials: IO
authors.lastname: Rosas
authors.forename: Souheil
authors.initials: S
authors.lastname: El-Chemaly
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D017564:Radiation Pneumonitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D011839:Radiation, Ionizing; D011878:Radiotherapy / Q000009:adverse effects*
chemical_list: D015415:Biomarkers