Combined Tlr2 and Tlr4 Deficiency Increases Radiation-Induced Pulmonary Fibrosis in Mice

NKT Deficient Mice are not Spared Lung Disease after Exposure to Thoracic Radiotherapy

“…-/-and C57BL/ 6J mice succumbed to disease at 22-26 weeks postirradiation which is similar to our published results of survival of identically treated female C57BL/6J mice (20)(21)(22)27). Male Ja18 -/-and C57BL/6J mice developed respiratory distress past the 26 week time point, and 10% of the male animals of each strain survived to the experimental end point of 35 weeks.…”

“…The lungs were then removed and the single left lobe was perfused with 10% buffered formalin and processed histologically. Lung sections of 5 lm were cut and stained with Masson's trichrome and the fibrosis score was calculated as the lung surface covered by fibrosis relative to the total lung surface using Image-Pro Plus software (Media Cybernetics, Rockville, MD) (20,21). To determine the degree of alveolitis, lung sections were stained with hematoxylin and eosin and evaluated semi-quantitatively through subjective scoring by an investigator blinded to strain and treatment.…”

“…Alveolitis was indicated by extent of airspace with cellular influx and thickening of alveolar walls. A score of 0-6 was given, 0 being no alveolitis and 6 being severe alveolitis, as in previous studies (21,22), based on the amount of lung tissue involved, without consideration to the extent of fibrosis. The BAL fluid was centrifuged (300g for 10 min at 48C) and the cellular pellet was re-suspended in 125 lL PBS.…”

“…Herein we investigated the response of Ja18 -/-mice (which exclusively lack type I NKT cells (19)] to thoracic radiation therapy. We compared the response of these mice to that of the background strain, C57BL/6J an inbred strain which we (20)(21)(22) and others (23,24) have shown succumbs to fibrosing alveolitis after thoracic irradiation. Although C57BL/6J mice are commonly used in pulmonary response studies, one group (25) suggests the response of this strain may have limitations.…”

Genetic Deficiency in Complement Component 4b Does Not Alter Radiation-Induced Lung Disease in Mice

“…Complement signaling can influence innate and adaptive immune responses (16,17), both of which have been implicated in the development of radiation-induced lung disease (18,19). In this study, we demonstrate that a deficiency in complement component C4b does not accelerate the onset of respiratory distress nor the amount of lung disease in mice exposed to whole-thorax irradiation.…”