Am. J. Respir. Cell Mol. Biol., Volume 23, Number 3, September, 2000 350-354

Differential Induction of Extracellular Glutathione Peroxidase and Nitric Oxide Synthase 2 in Airways of Healthy Individuals Exposed to 100% O₂ or Cigarette Smoke

Suzy A. A. Comhair, Mary Jane Thomassen, and Serpil C. Erzurum

Departments of Pulmonary and Critical Care Medicine, and Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio

Reactive oxygen species (ROS) is increased in the airway during the inhalation of 100% O₂ or cigarette smoke and participates in the development of tracheobronchitis. We hypothesized that inhaled ROS upregulates local extracellular ROS scavenging systems or reactive molecules, e.g., nitric oxide (NO). Extracellular glutathione peroxidase (eGPx) is synthesized by airway epithelium and alveolar macrophages, secreted into the surface epithelial lining fluid, and functions as a first-line defense against inhaled ROS. NO, produced by NO synthase 2 (NOS2), combines rapidly with ROS to form reactive nitrogen species (RNS). In this study, human airway epithelial cells and alveolar macrophages from healthy individuals before and after exposure to 100% O₂ for 12 h, or from cigarette-smoking individuals, were evaluated for eGPx and NOS2 messenger RNA (mRNA) expression. Hyperoxia increased NOS2 mRNA in airway epithelial cells by 2.5-fold but did not increase eGPx mRNA. In contrast, cigarette smoke upregulated eGPx mRNA over 2-fold in airway epithelial cells and alveolar macrophages but did not affect NOS2 expression. In vitro exposure of respiratory epithelial cells to ROS or RNS also increased eGPx expression. These findings define distinct molecular responses in the airway to different inhaled ROS, which likely influences the susceptibility of the airway to oxidative injury.

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