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

被引:91
作者
Sakamaki, F
Ishizaka, A
Urano, T
Sayama, K
Nakamura, H
Terashima, T
Waki, Y
Tasaka, S
Hasegawa, N
Sato, K
Nakagawa, N
Obata, T
Kanazawa, M
机构
[1] KEIO UNIV, SCH MED, DEPT MED, SHINJUKU KU, TOKYO 160, JAPAN
[2] ONO PHARMACEUT CO LTD, MINASE RES INST, OSAKA, JAPAN
关键词
D O I
10.1164/ajrccm.153.1.8542148
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 ravage (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 I-125-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 I-125-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.
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收藏
页码:391 / 397
页数:7
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