Role of type II pneumocytes in pathogenesis of radiation pneumonitis: dose response of radiation-induced lung changes in the transient high vascular permeability period.
We studied the dose response of pulmonary changes at 3 weeks after 1-25 Gy irradiation and we investigated the effects of an anti-inflammatory drug. Wistar rats were given a single dose of 1-25Gy irradiation to the thorax. Group one was treated with saline only, while group two was administered subcutaneously a combination of pentoxifylline (35 mg/kg) and dexamethasone (1 mg/kg) twice per week. Lungs were examined histochemically and number of neutrophile granulocytes, alveolar septal thickness, air/tissue ratio, number of alveoli per field, number of type II pneumocytes per alveolus, and occludin 1 expression were measured. A significant dose-dependent depletion of type II pneumocytes was found after irradiation with a dose of 1 Gy and higher. Alveolar neutrophils increased after 1 Gy with a dose dependency noted after 10-25Gy and alveolar septa thickening followed 5-25 Gy. A lower occludin 1 expression was observed in animals irradiated with the doses of 5 20 Gy, indicating an effect on vascular permeability. Anti-inflammatory therapy partially inhibited the increase of neutrophils at all radiation doses and the depletion of type II pneumocytes after doses of 1, 10, and 15 Gy. Occludin 1 did not decrease in the lungs of rats treated with the anti-inflammatory drugs as it did in most rats treated only with saline. Our results suggest that pneumocytes depletion is a major factor responsible for radiation pneumonitis development and that these changes may be compensated for provided radiation doses are below the threshold.
Osterreicher
Jan
J
Department of Radiobiology, Purkyne Military Medical Academy, Trebesska 1575, Hradec Králoré 50001, Czech Republic. osterreicher@pmfhk.cz
Pejchal
Jaroslav
J
Skopek
Jirí
J
Mokrỳ
Jaroslav
J
Vilasová
Zdena
Z
Psutka
Jan
J
Vávrová
Jirina
J
Mazurová
Yvona
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002199:Capillary Permeability / Q000528:radiation effects*; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004359:Drug Therapy, Combination; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology / Q000528:radiation effects; D062793:Occludin; D010431:Pentoxifylline / Q000627:therapeutic use; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D017564:Radiation Pneumonitis / Q000188:drug therapy / Q000473:pathology*; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D011837:Radiation-Protective Agents; D003907:Dexamethasone; D010431:Pentoxifylline