title: Hyperoxia accelerates Fas-mediated signaling and apoptosis in the lungs of Legionella pneumophila pneumonia.
abstract: BACKGROUND
  Oxygen supplementation is commonly given to the patients with severe pneumonia including Legionella disease. Recent data suggested that apoptosis may play an important role, not only in the pathogenesis of Legionella pneumonia, but also in oxygen-induced tissue damage. In the present study, the lethal sensitivity to Legionella pneumonia were compared in the setting of hyperoxia between wild-type and Fas-deficient mice.
  
  
  RESULTS
  C57BL/6 mice and B6.MRL-Faslpr mice characterized with Fas-deficiency were used in this study. After intratracheal administration of L. pneumophila, mice were kept in hyperoxic conditions (85-90% O2 conc.) in an airtight chamber for 3 days. Bone-marrow derived macrophages infected with L. pneumophila were also kept in hyperoxic conditions. Caspase activity and cytokine production were determined by using commercially available kits. Smaller increases of several apoptosis markers, such as caspase-3 and -8, were demonstrated in Fas-deficient mice, even though the bacterial burdens in Fas-deficient and wild type mice were similar. Bone-marrow derived macrophages from Fas-deficient mice were shown to be more resistant to Legionella-induced cytotoxicity than those from wild-type mice under hyperoxia.
  
  
  CONCLUSIONS
  These results demonstrated that Fas-mediated signaling and apoptosis may be a crucial factor in the pathogenesis of Legionella pneumonia in the setting of hyperoxia.
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University Faculty of Medicine, Tokyo 143-8540, Japan. kimsou@med.toho-u.ac.jp.
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Maeda
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kimura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi