Increased arginase activity contributes to airway remodelling in chronic allergic asthma

H. Maarsingh*, B. G. J. Dekkers, A. B. Zuidhof, I. S. T. Bos, M. H. Menzen, T. Klein, G. Flik, J. Zaagsma, H. Meurs

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

70 Citations (Scopus)

Abstract

Airway remodelling, characterised by increased airway smooth muscle (ASM) mass, subepithelial fibrosis, goblet cell hyperplasia and mucus gland hypertrophy, is a feature of chronic asthma. Increased arginase activity could contribute to these features via increased formation of polyamines and L-proline downstream of the arginase product L-ornithine, and via reduced nitric oxide synthesis.

Using the specific arginase inhitibor 2(S)-amino-6-boronohexanoic acid (ABH), we studied the role of arginase in airway remodelling using a guinea pig model of chronic asthma. Ovalbumin-sensitised guinea pigs were treated with ABH or PBS via inhalation before each of 12 weekly allergen or saline challenges, and indices of arginase activity, and airway remodelling, inflammation and responsiveness were studied 24 h after the final challenge.

Pulmonary arginase activity of repeatedly allergen-challenged guinea pigs was increased. Allergen challenge also increased ASM mass and maximal contraction of denuded tracheal rings, which were prevented by ABH. ABH also attenuated allergen-induced pulmonary hydroxyproline (fibrosis) and putrescine, mucus gland hypertrophy, goblet cell hyperplasia, airway eosinophilia and interleukin-13, whereas an increased L-ornithine/L-citrulline ratio in the lung was normalised. Moreover, allergen-induced hyperresponsiveness of perfused tracheae was fully abrogated by ABH.

These findings demonstrate that arginase is prominently involved in allergen-induced airway remodelling, inflammation and hyperresponsiveness in chronic asthma.

Original languageEnglish
Pages (from-to)318-328
Number of pages11
JournalEuropean Respiratory Journal
Volume38
Issue number2
DOIs
Publication statusPublished - Aug-2011

Keywords

  • Airway hyperresponsiveness
  • airway remodelling
  • eosinophils
  • fibrosis
  • goblet cells
  • polyamines
  • SMOOTH-MUSCLE-CELLS
  • NITRIC-OXIDE INHIBITION
  • INDUCED UP-REGULATION
  • GUINEA-PIG MODEL
  • S-NITROSYLATION
  • MUCUS SECRETION
  • IN-VITRO
  • HYPERRESPONSIVENESS
  • INFLAMMATION
  • LUNG

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