Neutrophil depletion inhibits airway hyperresponsiveness induced by ozone exposure

P. M. O'Byrne, E. H. Walters, B. D. Gold, H. A. Aizawa, L. M. Fabbri, S. E. Alpert, J. A. Nadel, M. J. Holtzman

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165 Scopus citations

Abstract

We studied whether ozone-induced hyperresponsiveness could be inhibited by neutrophil depletion in dogs. Responsiveness was assessed with dose-response curves of acetylcholine aerosol versus 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 x 103 per mm2 (mean ± SEM), and responsiveness before ozone did not change. Furthermore, increases in responsiveness and epithelial neutrophils did not occur after ozone. Six wk after stopping hydroxyurea, responsiveness and epithelial neutrophils increased markedly after ozone. The results suggest that ozone-induced hyperresponsiveness may depend on the mobilization of neutrophils into the airways.

Original languageEnglish
Pages (from-to)214-219
Number of pages6
JournalAmerican Review of Respiratory Disease
Volume130
Issue number2
DOIs
StatePublished - 1984

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