TY - JOUR
T1 - Effect of a specific neutrophil elastase inhibitor, ONO-5046, on endotoxin-induced acute lung injury
AU - Sakamaki, Fumio
AU - Ishizaka, Akitoshi
AU - Urano, Tetsuya
AU - Sayama, Koichi
AU - Nakamura, Hidetoshi
AU - Terashima, Takeshi
AU - Waki, Yasuhiro
AU - Tasaka, Sadatomo
AU - Hasegawa, Naoki
AU - Sato, Kiyoyuki
AU - Nakagawa, Naoki
AU - Obata, Takaaki
AU - Kanazawa, Minoru
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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U2 - 10.1164/ajrccm.153.1.8542148
DO - 10.1164/ajrccm.153.1.8542148
M3 - Article
C2 - 8542148
AN - SCOPUS:9044244530
SN - 1073-449X
VL - 153
SP - 391
EP - 397
JO - American Review of Respiratory Disease
JF - American Review of Respiratory Disease
IS - 1
ER -