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

Abstract

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 (alpha 1-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 alpha 1-PI elastase inhibitory activity, the immunologic concentration of alpha 1-PI, total protein, and albumin. The ratio of alpha 1-PI activity to its immunologic concentration was taken as the functional activity of alpha 1-PI, and possible changes in the amount of alpha 1-PI in the lung were assessed by examining the ratio of the immunologic concentration of alpha 1-PI to total protein. Neither of the NO2 exposure protocols resulted in a decrease in the functional activity of alpha 1-PI, nor were there alterations in the immunologic levels of alpha 1-PI. These data suggest that short-term exposures to low levels of NO2 do not result in a lung-localized deficiency of active alpha 1-PI, which has been hypothesized to be a contributing factor in the pathogenesis of emphysema.