Pathogenesis of nitrogen dioxide-induced respiratory lesions in reference to respiratory clearance of inhaled particulates

The pathogenesis of NO2-induced respiratory disease and the effect of NO2 on respiratory clearance of 51Cr2O3 were studied. Young adult female mice were exposed to a 51Cr2O3 aerosol, followed by a daily exposure to either 30 ppm NO2 for 2 wk or 60 ppm NO2 for 2 wk or a single exposure to 170 ppm NO2. Exposure to 30 ppm NO2 had a minimal histopathologic effect on respiratory tract tissue. Exposure to 60 ppm NO2 produced marked histopathologic effects, which were subsequently resolved. Exposure to 170 ppm NO2 produced permanent histopathologic lesions. In mice exposed to concentrations of NO2 that produced minimal histopathologic effects, respiratory clearance of 51Cr2O3 was similar to that in unexposed mice. When mice were exposed to concentrations of NO2 that produced permanent tissue damage, prolonged impairment of respiratory clearance of 51Cr2O3 was observed, despite resolution of edema produced by inhalation of NO2. At concentrations of NO2 that produced marked edema and histopathologic effects that were resolved despite repeated NO2 exposure, there was an initial marked impairment of respiratory clearance, then an accelerated rate of clearance, and finally a clearance rate similar to that of unexposed mice. The time during which accelerated clearance occurred was well correlated with the time at which the histopathologic lesions was observed to regress.