Effect of a specific neutrophil elastase inhibitor, ONO-5046, on endotoxin-induced acute lung injury

Fumio Sakamaki, Akitoshi Ishizaka, Tetsuya Urano, Koichi Sayama, Hidetoshi Nakamura, Takeshi Terashima, Yasuhiro Waki, Sadatomo Tasaka, Naoki Hasegawa, Kiyoyuki Sato, Naoki Nakagawa, Takaaki Obata, Minoru Kanazawa

研究成果: Article査読

105 被引用数 (Scopus)

抄録

Because excessive neutrophil elastase (NE) activity is involved in the pathogenesis of acute lung injury, we speculated that administering anti-NE might prevent lung injury. In a guinea pig model of acute lung injury induced by Escherichia coli endotoxin (lipopolysaccharide [LPS]), we investigated the effect of ONO-5046, a low-molecular-weight and specific inhibitor of NE. ONO- 5046 produced concentration-dependent inhibition of guinea pig NE, whereas there were no inhibitory effects on neutrophil chemotaxis or the expression of adhesion molecules in endothelial cells. Detectable NE activity in bronchoalveolar lavage (BAL) fluid was present in the LPS-alone group. No NE activity in BAL fluid was detected in the LPS + ONO-5046 groups. Neutrophil counts in BAL fluid, the lung tissue wet to dry weight ratio, and the lung tissue or BAL fluid to plasma ratio of 125I-albumin were increased in the LPS-alone group as compared with the saline group (p < 0.05). In the LPS + ONO-5046 group, neutrophil counts in BAL fluid, the lung tissue wet to dry weight ratio and BAL fluid to plasma ratio of 125I-albumin were decreased as compared with the LPS-alone group (p < 0.05). These data suggest that ONO- 5046 can attenuate LPS-induced acute lung injury.

本文言語English
ページ(範囲)391-397
ページ数7
ジャーナルAmerican journal of respiratory and critical care medicine
153
1
DOI
出版ステータスPublished - 1996
外部発表はい

ASJC Scopus subject areas

  • 呼吸器内科
  • 集中医療医学

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