Neutrophil elastase inhibitor, ONO-5046 suppresses ozone-induced airway mucus hypersecretion in guinea pigs

Hiroko Nogami, Hisamichi Aizawa, Koichiro Matsumoto, Hiroyuki Nakano, Hiroshi Koto, Hiroyuki Miyazaki, Takahito Hirose, Sankei Nishima, Nobuyuki Hara

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Abstract

To investigate the role of neutrophil elastase in ozone-induced airway hypersecretion, we measured goblet cell secretion by using a semiquantitative morphometric technique in guinea pigs. The magnitude of mucus discharge was estimated from the mucus score, which is inversely related to the degree of mucus discharge in histological sections of trachea stained for mucus glycoprotein with periodic acid Schiff/Alcian blue. Mucus hypersecretion of goblet cells was induced by ozone exposure and persisted for up to 5 h after exposure. Pretreatment with N-[2-{4-(2,2-dimetyl-propionyloxy) phenyl-sulfonylamino} benzoyl] aminoacetic acid (ONO-5046), a specific neutrophil elastase inhibitor (200 mg/kg, intraperitoneally), significantly inhibited goblet cell hypersecretion both just after and 5 h after ozone-exposure, but the latter inhibition was not complete. In bronchoalveolar lavage fluid, ozone exposure significantly increased the number of neutrophils just after and 5 h after exposure, while ONO-5046 significantly inhibited the increase in neutrophils only 5 h after ozone-exposure. These results indicate that neutrophil elastase may play an important role in the ozone-induced tracheal goblet cell hypersecretion and influx of neutrophils. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)197-202
Number of pages6
JournalEuropean Journal of Pharmacology
Volume390
Issue number1-2
DOIs
Publication statusPublished - Feb 25 2000

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Secretory Proteinase Inhibitory Proteins
Ozone
Mucus
Guinea Pigs
Goblet Cells
Leukocyte Elastase
Neutrophils
Alcian Blue
Periodic Acid
Bronchoalveolar Lavage Fluid
Trachea
Glycine
sivelestat

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Neutrophil elastase inhibitor, ONO-5046 suppresses ozone-induced airway mucus hypersecretion in guinea pigs. / Nogami, Hiroko; Aizawa, Hisamichi; Matsumoto, Koichiro; Nakano, Hiroyuki; Koto, Hiroshi; Miyazaki, Hiroyuki; Hirose, Takahito; Nishima, Sankei; Hara, Nobuyuki.

In: European Journal of Pharmacology, Vol. 390, No. 1-2, 25.02.2000, p. 197-202.

Research output: Contribution to journalArticle

Nogami, Hiroko ; Aizawa, Hisamichi ; Matsumoto, Koichiro ; Nakano, Hiroyuki ; Koto, Hiroshi ; Miyazaki, Hiroyuki ; Hirose, Takahito ; Nishima, Sankei ; Hara, Nobuyuki. / Neutrophil elastase inhibitor, ONO-5046 suppresses ozone-induced airway mucus hypersecretion in guinea pigs. In: European Journal of Pharmacology. 2000 ; Vol. 390, No. 1-2. pp. 197-202.
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