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Examining the role of arginase in air pollution-induced exacerbation of asthma

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Allergy, Asthma & Clinical Immunology20106 (Suppl 3) :P5

  • Published:


  • Arginase
  • Methacholine
  • Airway Hyperresponsiveness
  • Arginase Activity
  • Allergic Airway Inflammation


The arginase isozymes (arginase 1 and 2), convert L-arginine into L-ornithine and urea, and thus compete with the nitric oxide synthase isozymes for substrate. We have previously shown that arginase 1 expression is upregulated in human asthma and plays a functional role in airways hyperresponsiveness (AHR) in an animal model of allergic airways inflammation. Ambient particles and ozone are major constituents of urban air pollution and contribute to asthma exacerbations. However, the mechanisms underlying the exacerbation of allergic airways disease by air pollution remain to be elucidated. There is evidence that arginase expression is augmented in cigarette smoking asthmatics. We tested the hypothesis that arginase is involved in the exacerbation of respiratory symptoms in response to air pollution in animal models of allergic airways inflammation.


We used sub-acute (16-day) and chronic (12-week) murine models of ovalbumin (OVA)-induced allergic airways inflammation as models of asthma. All mice were sensitized to OVA, and then randomized to aerosol challenge with PBS (control; OVA/PBS) or OVA (allergic airways inflammation; OVA/OVA). Twenty-four hours after the final OVA or PBS challenge, mice underwent a combined exposure to concentrated ambient fine particles plus ozone (CAP+O3), or filtered air. Following exposure, mice were treated with either the arginase inhibitor S-boronoethyl l-cysteine (BEC; 40 μg/g b.w.), or vehicle (PBS), by direct nebulization into the airways. After determination of the airways responsiveness to methacholine using the flexiVent, tissues were harvested for Western blotting, activity testing and immunohistochemistry.


Exposure to CAP+O3 augmented the AHR in the OVA/OVA mice with no significant effect on the OVA/PBS controls in both the sub-acute and chronic models. Expression of arginase 1 and total arginase activity were significantly augmented in OVA/OVA mice exposed to CAP+O3, compared to filtered air. Immunohistochemistry revealed that arginase 1 expression was specifically up-regulated in the peribronchiolar region following CAP+O3 exposure in OVA/OVA mice. Treatment with BEC significantly reduced the pollution-induced AHR in CAP+O3-exposed OVA/OVA mice in both the sub-acute and chronic murine models to control levels.


This study demonstrates that arginase 1 is up-regulated following environmental exposures in murine models of allergic airways inflammation. Attenuation of airways hyperresponsiveness by arginase inhibition suggests that this pathway is a promising candidate for future therapies to prevent or treat air pollution-induced exacerbation of allergic symptoms.



This study was supported by AllerGen NCE, National Sanitarium Association, St. Michael's Hospital Research Centre. MN is a recipient of CIHR and OTS Doctoral Awards.

Authors’ Affiliations

Institutes of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada
Divisions of Occupational and Respiratory Medicine, University of Toronto, Toronto, Canada
Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
The Gage Occupational and Environmental Health Unit, St. Michael's Hospital, Toronto, Canada
Occupational and Environmental Health Program, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
Physiology and Experimental Medicine, Division of Respiratory Medicine, The Hospital for Sick Children., University of Toronto, Toronto, Canada


© North et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.