Neutrophil Depletion Inhibits Airway Hyperresponsiveness Induced by Ozone Exposure

Abstract

Ozone-induced hyperresponsiveness may be inhibited by neutrophil depletion in dogs. Responsiveness was assessed with dose-response curves of acetylcholine aerosol vs. pulmonary resistance; depletion was assessed by counting neutrophils in venous blood and in biopsies of the airway epithelium. Responsiveness and neutrophil numbers were determined 5 days and 1 day before ozone and 1 h after ozone (3.0 ppm, 2 h) in 6 untreated dogs and in 6 dogs treated with hydroxyurea (200 mg/kg daily for 5 days starting 5 days before ozone). In untreated dogs, responsiveness and neutrophil numbers 5 days and 1 day before ozone did not change, but responsiveness and epithelial neutrophils increased markedly after ozone. In treated dogs, circulating neutrophils decreased from 8.9 .+-. 2.2 to 0.6 .+-. 0.01 .times. 103/mm3 (mean), and responsiveness before ozone did not change. Increases in responsiveness and epithelial neutrophils did not occur after ozone. Six wk after stopping hydroxyurea, responsiveness and epithelial neutrophils increased markedly after ozone. Ozone-induced hyperresponsiveness may depend on the mobilization of neutrophils into the airways.