title: New insights into the molecular pathology of radiation-induced pneumopathy.
abstract: OBJECTIVE
  Pneumonitis and fibrosis constitute dose-limiting side effects of thorax or total body irradiation. An improved understanding of the underlying mechanisms is a prerequisite for the development of effective radioprotective strategies. Here we characterized the behavior of resident and immune cells in a murine model of radiation-induced pneumopathy.
  
  
  METHODS
  Wild type (WT) or RAG-2 deficient C57BL/6 mice received 15 Gray of (hemi)-thorax irradiation in a single dose. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected at defined time points post-irradiation for the determination of apoptosis, microvascular injury, and histological and immunohistochemical analyses.
  
  
  RESULTS
  Higher albumin levels and increased apoptosis were detected in the BALF 21 days after irradiation, indicative for delayed damage to resident cells. Irradiation also induced time-dependent changes in the BALF cytokine profile, the recruitment of activated T-cells into the lung and the formation of lipid-loaded resident cells. Lung fibrosis occurred earlier in RAG-2(-/-) mice, which lack mature T and B cells, compared to WT mice.
  
  
  CONCLUSIONS
  Thorax irradiation triggers a delayed disturbance of tissue integrity and lipid metabolism in the lung. Activated T-lymphocytes infiltrating the lung tissue upon thorax irradiation participate in the protection of the lung from radiation-induced fibrosis.
authors: Institute of Cell Biology (Cancer Research), University Hospital Essen, Germany.
authors: Federica
authors: F
authors: Cappuccini
authors: Therese
authors: T
authors: Eldh
authors: Dunja
authors: D
authors: Bruder
authors: Marcus
authors: M
authors: Gereke
authors: Holger
authors: H
authors: Jastrow
authors: Klaus
authors: K
authors: Schulze-Osthoff
authors: Ute
authors: U
authors: Fischer
authors: David
authors: D
authors: Köhler
authors: Martin
authors: M
authors: Stuschke
authors: Verena
authors: V
authors: Jendrossek
mesh_terms: D000418:Albumins / Q000378:metabolism / Q000528:radiation effects; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D008168:Lung / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D057089:Pathology, Molecular / Q000379:methods*; D009195:Peroxidase / Q000378:metabolism / Q000528:radiation effects; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011829:Radiation Dosage; D017564:Radiation Pneumonitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D012016:Reference Values; D013909:Thorax / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D000418:Albumins; D016207:Cytokines; D009195:Peroxidase