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

1. Ozone inhalation causes airway hyper-responsiveness and airway inflammation in dogs. The purpose of this study was to determine whether these effects are associated with increases in oxygen radical production from bronchoalveolar lavage (BAL) cells. 2. Twelve randomly selected dogs were studied twice, 4 weeks apart. On each study day, acetylcholine (ACh) airway responsiveness was measured before and Ih after ozone (3 p.p.m., 30 min) or dry air inhalation, followed by BAL. The response to ACh was expressed as the concentration causing an increase in lung 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 measured by luminol-enhanced chemiluminescence in a luminometer at 37 degrees C. 3. Ozone inhalation caused airway hyper-responsiveness. The concentration 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 ozone (P < 0.0001). Spontaneous chemiluminescence area under the curve (AUC) 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 chemiluminescence AUC from 18.97 mV (10 min; %S.E.M., 1.18) after dry air to 144.03 mV (10 min; %S.E.M., 1.45) after ozone (P = 0.0001). The increase in PMA-stimulated chemiluminescence was significantly correlated with ozone-induced ACh airway hyper-responsiveness (r = 0.83, P < 0.001). 4. These results indicate that inhaled ozone increases oxygen radical release from BAL cells and suggest that oxygen radicals are important in causing ozone-induced airway hyper-responsiveness