Inhalation of Nitrogen Dioxide Fails to Reduce the Activity of Human Lung Alpha-1-Proteinase Inhibitor

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Healthy, nonsmoking human volunteers were exposed to environmentally relevant concentrations of NO2 followed by bronchoalveolar lavage (BAL) to study whether NO2 exposure decreases the functional activity of alpha-1-proteinase inhibitor (α-PI) in the lung. Two 3-h exposure protocols with intermittent exercise were employed and BAL was performed 3.5 h after exposure. The first exposure protocol with nine subjects involved three 2-ppm “peaks” with a 0.05 ppm background, whereas the second protocol with 15 subjects was a continuous exposure to 1.5 ppm NO2. All subjects were randomly exposed to either air or NO2, with at least a 2-wk interval between treatments, and the BAL fluids obtained after air exposure served as the controls. The BAL fluids were analyzed for α1-PI elastase inhibitory activity, the immunologic concentration of α1-PI, total protein, and albumin. The ratio of α1-PI activity to its immunologic concentration was taken as the functional activity of α1-PI, and possible changes in the amount of α1-PI in the lung were assessed by examining the ratio of the immunologic concentration of α1-PI to total protein. Neither of the NO2 exposure protocols resulted in a decrease in the functional activity of α1-PI, nor were there alterations in the immunologie levels of α1-PI. These data suggest that short-term exposures to low levels of NO2 do not result in a lung-localized deficiency of active α1-PI, which has been hypothesized to be a contributing factor in the pathogenesis of emphysema.

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