Antioxidant responses to acute ozone challenge in the healthy human airway

The aim of the study was to characterize ozone-induced antioxidant responses in the human airway, including the resident leukocyte population, bronchial mucosa, and respiratory-tract lining fluids. Fifteen healthy subjects were exposed to 0.2 ppm ozone for 2 h, with bronchial wash, bronchoalveolar lavage, and biopsy sampling performed 6 h postexposure. Nasal lavage was also performed at multiple time points pre- and postexposure to evaluate responses during the actual exposure period. During the ozone challenge significant losses of nasal lining fluid urate and vitamin C were observed, which resolved 6 h postexposure. At this time point, increased numbers of neutrophils and enhanced concentrations of total glutathione, vitamin C, and urate were seen in bronchial airway lavages. In bronchoalveolar lavage, increased concentrations of total glutathione, vitamin C, urate, alpha-tocopherol, and extracellular superoxide dismutase occurred 6 h post ozone. In alveolar leukocytes significant losses of glutathione were observed, whereas ascorbate concentrations in endobronchial mucosal biopsies were elevated after ozone at this time. These data demonstrate that ozone elicits a broad spectrum of airway antioxidant responses, with initial losses of vitamin C and urate followed by a phase of augmentation of low-molecular-weight antioxidant concentrations at the air-lung interface. The temporal association between the increased RTLF glutathione following ozone and the loss of this thiol from macrophages implies a mobilization to the lung surface, despite the absence of a quantitative association. We propose this constitutes an acute protective adaptation to ozone.