Irradiation-induced pneumonitis mediated by the CD95/CD95-ligand system.
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.
Heinzelmann
Frank
F
Department of Radiation Oncology, University of Tuebingen, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany.
Jendrossek
Verena
V
Lauber
Kirsten
K
Nowak
Kerstin
K
Eldh
Therese
T
Boras
Ruzica
R
Handrick
Rene
R
Henkel
Marco
M
Martin
Christian
C
Uhlig
Stefan
S
Köhler
David
D
Eltzschig
Holger K
HK
Wehrmann
Manfred
M
Budach
Wilfried
W
Belka
Claus
C
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*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors