BIOCHEMICAL EFFECTS OF ACUTE AND SUBACUTE NITROGEN-DIOXIDE EXPOSURE IN RAT LUNG AND BRONCHOALVEOLAR LAVAGE FLUID

The pulmonary inflammatory response to NO2 exposure was measured by ev aluating a series of biochemical and cellular parameters in rat bronch oalveolar lavage fluid. Animals were exposed to 9 mg/m(3) (5 ppm) or 1 8 mg/m(3) (10 ppm) of the gas for 24 h or 7 days. After bronchoalveola r lavage collection, a differential count of polymorphonuclear leukocy tes, macrophages, and lymphocytes was done. A significant increase in polymorphonuclear leukocytes was found after 24 h of exposure, and aft er 7 days the number of macrophages increased significantly. After 7 d ays of exposure to 9 mg/m(3) of NO2 (a dose that under our conditions did not induce migration of cells in the bronchoalveolar spaces) the e x vivo phorbol myristate acetate-induced superoxide anion production b y resident cells was inhibited. After 24 h and 7 days of exposure to 1 8 mg/m(3) of NO2, phorbol myristate acetate-induced superoxide anion p roduction was lower than in the control group. The migration of polymo rphonuclear leukocytes in the bronchoalveolar lavage fluid was not ass ociated with any real increase in elastase. However, there was a dose- and time-dependent increase in alpha 1-proteinase inhibitor in respon se to both 9 and 18 mg/m(3) of NO2. Total glutathione was significantl y increased in blood by 24 h treatment with 9 or 18 mg/m(3) of NO2, wh ereas blood oxidized glutathione was not affected. In lung tissue we o bserved only a significant increase of oxidized glutathione after 24 h of exposure to 9 and 18 mg/m(3) of NO2. These data suggest that many biochemical and cellular parameters are altered after acute or subacut e exposure to relatively high doses of NO2, especially in the first 24 h. The increase of or alpha 1-proteinase inhibitor and blood glutathi one can be considered a prompt protective response to the toxic injury .