Differential induction of extracellular glutathione peroxidase and nitric oxide synthase 2 in airways of healthy individuals exposed to 100% O-2 or cigarette smoke

Reactive oxygen species (ROS) is increased in the airway during the inhalat ion of 100% O-2 or cigarette smoke and participates in the development of t racheobronchitis. We hypothesized that inhaled ROS upregulates local extrac ellular ROS scavenging systems or reactive molecules, e.g., nitric oxide (N O). Extracellular glutathione peroxidase (eGPx) is synthesized by airway ep ithelium and alveolar macrophages, secreted into the surface epithelial lin ing fluid, and functions as a first-line defense against inhaled ROS, NO, p roduced by NO synthase 2 (NOS2), combines rapidly with ROS to form reactive nitrogen species (RNS), In this study, human airway epithelial cells and a lveolar macrophages from healthy individuals before and after exposure to 1 00% O-2 for 12 h, or from cigarette-smoking individuals, were evaluated for eGPx and NOS2 messenger RNA (mRNA) expression. Hyperoxia increased NOS2 mR NA in airway epithelial cells by 2.5-fold but did not increase eGPx mRNA. I n contrast, cigarette smoke upregulated eGPx mRNA over 2-fold in airway epi thelial cells and alveolar macrophages but did not affect NOS2 expression. In vitro exposure of respiratory epithelial cells to ROS or RNS also increa sed eGPx expression. These findings define distinct molecular responses in the airway to different inhaled ROS, which likely influences the susceptibi lity of the airway to oxidative injury.