Effect of a cysteinyl leukotriene receptor antagonist on experimental emphysema and asthma combined with emphysema

Genyo Ikeda, Nobuaki Miyahara, Hikari Koga, Yasuko Fuchimoto, Koichi Waseda, Etsuko Kurimoto, Akihiko Taniguchi, Yasushi Tanimoto, Mikio Kataoka, Mitsune Tanimoto, Arihiko Kanehiro

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The incidence of overlapping bronchial asthma and chronic obstructive pulmonary disease has increased in recent years. Cysteinyl leukotrienes (CysLTs) play an important role in asthma, and the type 1 CysLT receptor (CysLT 1R) is expressed by many inflammatory cells. We evaluated the effect of montelukast, a CysLT1R antagonist, on mouse models of asthma, porcine pancreatic elastase (PPE)-induced emphysema, and asthma combined with emphysema. Mice were sensitized with ovalbumin (OVA) on Days 0 and 14 and subsequently challenged with OVA on Days 28, 29, and 30. Pulmonary emphysema was induced by intratracheal instillation of PPE on Day 25. Mice were treated subcutaneously with montelukast or vehicle from Day 25 to Day 31. Airway hyperresponsiveness (AHR), static compliance; the number of inflammatory cells, the levels of cytokines, chemokines, LTs, and perforin in the bronchoalveolar lavage fluid, and the quantitative morphometry of lung sections were analyzed on Day 32. Treatment with montelukast significantly attenuated the AHR and eosinophilic airway inflammation in OVA-sensitized and OVA-challenged mice. Administration of montelukast significantly reduced the AHR, static compliance, and neutrophilic airway inflammation, while attenuating emphysematous lung changes, in PPE-treated mice. In PPE-treated mice subjected to allergen sensitization and challenges, montelukast significantly suppressed the AHR, static compliance, and eosinophilic and neutrophilic airway inflammation in addition to the development of experimentally induced emphysema in the lungs. Our data suggest that CysLT1R antagonists may be effective in ameliorating the consequences of PPE-induced lung damage and the changes that follow allergen sensitization and challenges.

Original languageEnglish
Pages (from-to)18-29
Number of pages12
JournalAmerican journal of respiratory cell and molecular biology
Volume50
Issue number1
DOIs
Publication statusPublished - Jan 2014

Keywords

  • Asthma
  • Chronic obstructive pulmonary disease
  • Cysteinyl leukotriene
  • Cysteinyl leukotriene receptor
  • Overlap of asthma and chronic obstructive pulmonary disease

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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