OZONE-INDUCED OXYGEN RADICAL RELEASE FROM BRONCHOALVEOLAR LAVAGE CELLS AND AIRWAY HYPERRESPONSIVENESS IN DOGS

1. Ozone inhalation causes airway hyper-responsiveness and airway infl ammation in dogs. The purpose of this study was to determine whether t hese effects are associated with increases in oxygen radical productio n from bronchoalveolar lavage (BAL) cells. 2. Twelve randomly selected dogs were studied twice, 4 weeks apart. On each study day, acetylchol ine (ACh) airway responsiveness was measured before and Ih after ozone (3 p.p.m., 30 min) or dry air inhalation, followed by BAL. The respon se to ACh was expressed as the concentration causing an increase in lu ng resistance of 5 cmH(2)O l(-1) s(-1) above baseline. Spontaneous and phorbol myristate acetate (PMA) (2.4 mu mol l(-1))-stimulated oxygen radical release from washed BBL cells (4 x 10(6) cells ml(-1)) was mea sured by luminol-enhanced chemiluminescence in a luminometer at 37 deg rees C. 3. Ozone inhalation caused airway hyper-responsiveness. The co ncentration of ACh causing an increase in lung resistance of 5 cmH(2)O l(-1) s(-1) (the 'provocative' concentration) fell from 4.68 mg ml(-1 ) (%S.E.M., 1.43) before, to 0.48 mg ml(-1) (%S.E.M., 1.60) after ozon e (P < 0.0001). Spontaneous chemiluminescence area under the curve (AU C) significantly increased after ozone from 4.08 mV (10 min) (%S.E.M., 1.28) after dry air to 8.25 mV (10 min; %S.E.M., 1.09) after ozone (P = 0.007). Ozone inhalation also increased PMA-stimulated chemilumines cence AUC from 18.97 mV (10 min; %S.E.M., 1.18) after dry air to 144.0 3 mV (10 min; %S.E.M., 1.45) after ozone (P = 0.0001). The increase in PMA-stimulated chemiluminescence was significantly correlated with oz one-induced ACh airway hyper-responsiveness (r = 0.83, P < 0.001). 4. These results indicate that inhaled ozone increases oxygen radical rel ease from BAL cells and suggest that oxygen radicals are important in causing ozone-induced airway hyper-responsiveness