Role of neutrophil elastase in ozone-induced airway responses in guinea- pigs

K. Matsumoto, H. Aizawa, H. Inoue, H. Koto, H. Nakano, N. Hara

研究成果: Contribution to journalArticle査読

30 被引用数 (Scopus)

抄録

Ozone-induced airway hyperresponsiveness occurs concurrently with neutrophilic inflammation and epithelial injury in various species including humans. The mechanism of neutrophil-induced airway hyperresponsiveness, however, has not yet been fully clarified. Neutrophil elastase (NE) is a multipotent protease released from activated neutrophils, which may play a role in ozone-induced airway hyperresponsiveness. In order to address this issue, the effects of ONO-5046, a specific NE inhibitor, were investigated in ozone-exposed guinea-pigs. Awake animals were exposed to ozone at 3 parts per million for 2 h, airway responsiveness to acetylcholine (ACh) measured and examination of bronchoalveolar lavage fluid (BALF) performed. Ozone exposure increased airway responsiveness to both inhaled and intravenous ACh, the concentration of NE in BALF and the number of neutrophils and airway epithelial cells in BALF. Although pretreatment with ONO-5046 (200 mg·kg- 1, i.p.) had no effect on these changes immediately after the exposure, it significantly inhibited airway hyperresponsiveness to inhaled ACh, whilst decreasing the number of neutrophils and epithelial cells in BALF 3-5 h after the exposure. In contrast, ONO-5046 showed no significant effect on airway hyperresponsiveness to intravenous ACh at any time. These results suggest that neutrophil elastase contributes to ozone-induced airway hyperresponsiveness developing during the hours after exposure, presumably by means of inducing epithelial injury.

本文言語英語
ページ(範囲)1088-1094
ページ数7
ジャーナルEuropean Respiratory Journal
14
5
DOI
出版ステータス出版済み - 1999

All Science Journal Classification (ASJC) codes

  • 呼吸器内科

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