title: Irradiation-induced pneumonitis mediated by the CD95/CD95-ligand system.
abstract: Pneumonitis is a dose-limiting side effect of radiotherapy. However, the underlying mechanisms of irradiation-induced pneumonitis are unclear. Several observations suggest that the CD95/CD95-ligand (CD95L) system is involved in this process. Therefore, we examined the development of pneumonitis in CD95- and CD95L-deficient and wild-type mice after single irradiation with 0 or 12.5 Gy by measuring breathing frequency, pulmonary resistance, and histopathologic changes. Although wild-type mice developed pathognomonic alterations characteristic of pneumonitis (judged by alveolar wall thickness, interstitial edema, and interstitial and peribronchial inflammation) that paralleled increased breathing frequency ratio on days 5-70 (P < .03) with a maximum at day 37 (12.5 Gy, mean ratio = 1.05, 95% confidence interval [CI] = 1.01 to 1.08; P = .004 versus 0 Gy, mean ratio = 0.997, 95% CI = 0.976 to 1.02; P = .05) and pulmonary resistance (day 42, 12.5 Gy, mean = 0.51, 95% CI = 0.44 to 0.58 versus 0 Gy, mean = 0.40, 95% CI = 0.32 to 0.47; P = .03) after irradiation, no such changes were detected in CD95- or CD95L-deficient mice. This report demonstrates for the first time, to our knowledge, that the CD95/CD95L system is important for the development of irradiation-induced pneumonitis.
authors.affiliation: Department of Radiation Oncology, University of Tuebingen, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Heinzelmann
authors.forename: Verena
authors.initials: V
authors.lastname: Jendrossek
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.forename: Kerstin
authors.initials: K
authors.lastname: Nowak
authors.forename: Therese
authors.initials: T
authors.lastname: Eldh
authors.forename: Ruzica
authors.initials: R
authors.lastname: Boras
authors.forename: Rene
authors.initials: R
authors.lastname: Handrick
authors.forename: Marco
authors.initials: M
authors.lastname: Henkel
authors.forename: Christian
authors.initials: C
authors.lastname: Martin
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlig
authors.forename: David
authors.initials: D
authors.lastname: Köhler
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
authors.forename: Manfred
authors.initials: M
authors.lastname: Wehrmann
authors.forename: Wilfried
authors.initials: W
authors.lastname: Budach
authors.forename: Claus
authors.initials: C
authors.lastname: Belka
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D053222:Fas Ligand Protein; D005260:Female; D008168:Lung / Q000378:metabolism / Q000503:physiopathology / Q000528:radiation effects*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D011832:Radiation Injuries / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D011839:Radiation, Ionizing; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D048069:Tumor Necrosis Factors / Q000172:deficiency / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors