The objective of this proposal is to identify the biochemical mechanisms of tolerance and adaptation exhibited by the lung after exposure to the oxidant gas ozone. It is our hypothesis that the Type II pneumocyte is a critical target cell for alveolar epithelial injury after oxidant gas exposure. As such, we propose that structural and functional changes in Type II pneumocytes will develop during oxidant gas exposure and continue after cessation of exposure. We plan to isolate Type II pneumocytes from the rabbit lung during and after exposure to ozone. We postulate that functional changes induced by oxidant gas exposure will include increased intracellular activities of antioxidant enzymes and altered levels of surfactant phospholipid synthesis. We will measure activities of key enzymes involved in surfactant synthesis and characterize the intensity of enzyme changes to varying sublethal doses of ozone. We will characterize the time course for the development of protective antioxidant enzyme induction within isolated Type II pneumocytes. We propose that oxidant gas induced lung injury can be characterized quantitatively and temporally by determining levels of released intracellular protein obtained from pulmonary lavage. We will quantitate markers of cellular injury released into lavage fluid in our rabbit model. We will also quantitate changes in cell populations in lavage fluid as a measure of airway inflammation. Changes in the intensity and duration of airway inflammation will be correlated with induction of intracellular enzymes. The technique developed in our analysis of pulmonary lavage fluid should have potential application for use in human exposure studies. An understanding of the mechanisms of injury to pulmonary tissues and biological responses under different exposure conditions is important in our determination of the causes of chronic lung damage that accompanies exposure to oxidant gases. In addition, such studies should help us to establish realistic environmental standards for the various oxidant pollutants.
| Bauer, M A; Utell, M J; Morrow, P E et al. (1986) Inhalation of 0.30 ppm nitrogen dioxide potentiates exercise-induced bronchospasm in asthmatics. Am Rev Respir Dis 134:1203-8 |
