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

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)391-397
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume153
Issue number1
Publication statusPublished - 1996
Externally publishedYes

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Secretory Proteinase Inhibitory Proteins
Acute Lung Injury
Bronchoalveolar Lavage Fluid
Endotoxins
Leukocyte Elastase
Lipopolysaccharides
Neutrophils
Pulmonary Edema
Albumins
Guinea Pigs
Weights and Measures
Lung Injury
Chemotaxis
sivelestat
Endothelial Cells
Molecular Weight

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Sakamaki, F., Ishizaka, A., Urano, T., Sayama, K., Nakamura, H., Terashima, T., ... Kanazawa, M. (1996). Effect of a specific neutrophil elastase inhibitor, ONO-5046, on endotoxin-induced acute lung injury. American Journal of Respiratory and Critical Care Medicine, 153(1), 391-397.

Effect of a specific neutrophil elastase inhibitor, ONO-5046, on endotoxin-induced acute lung injury. / Sakamaki, Fumio; Ishizaka, Akitoshi; Urano, Tetsuya; Sayama, Koichi; Nakamura, Hidetoshi; Terashima, Takeshi; Waki, Yasuhiro; Tasaka, Sadatomo; Hasegawa, Naoki; Sato, Kiyoyuki; Nakagawa, Naoki; Obata, Takaaki; Kanazawa, Minoru.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 153, No. 1, 1996, p. 391-397.

Research output: Contribution to journalArticle

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 1996, 'Effect of a specific neutrophil elastase inhibitor, ONO-5046, on endotoxin-induced acute lung injury', American Journal of Respiratory and Critical Care Medicine, vol. 153, no. 1, pp. 391-397.
Sakamaki, Fumio ; Ishizaka, Akitoshi ; Urano, Tetsuya ; Sayama, Koichi ; Nakamura, Hidetoshi ; Terashima, Takeshi ; Waki, Yasuhiro ; Tasaka, Sadatomo ; Hasegawa, Naoki ; Sato, Kiyoyuki ; Nakagawa, Naoki ; Obata, Takaaki ; Kanazawa, Minoru. / Effect of a specific neutrophil elastase inhibitor, ONO-5046, on endotoxin-induced acute lung injury. In: American Journal of Respiratory and Critical Care Medicine. 1996 ; Vol. 153, No. 1. pp. 391-397.
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