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

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

72 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)318-328
Aantal pagina's11
TijdschriftEuropean Respiratory Journal
Volume38
Nummer van het tijdschrift2
DOI's
StatusPublished - aug-2011

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