Volume 7 Supplement 2

Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2011

Open Access

Role of proteinase-activated receptor-2 in allergic sensitization to house dust mite allergens

  • Courtney Davidson1,
  • Danny Polley2,
  • Muhammad Asaduzzaman1,
  • Narcy Arizmendi1,
  • John R Gordon3,
  • Morley D Hollenberg2 and
  • Harissios Vliagoftis1
Allergy, Asthma & Clinical Immunology20117(Suppl 2):A30

DOI: 10.1186/1710-1492-7-S2-A30

Published: 14 November 2011

Background

A number of common aeroallergens have serine proteinase activity, which is important for allergic sensitization. House dust mite (HDM), and other allergens with serine proteinase activity activate Protease-Activated Receptor-2 (PAR-2). We have shown that PAR-2 activation in the airways leads to allergic sensitization to concomitantly inhaled antigens, implicating PAR-2 in the pathogenesis of asthma. We hypothesized that PAR-2 activation in the airways by HDM allergens is important for the development of allergic sensitization.

Methods

HDM extract was administered to mice intranasally for 5 consecutive days to induce allergic sensitization. One group of mice received a blocking anti-PAR-2 antibody intranasally before each HDM administration.

Results

Administration of the PAR-2 blocking antibody decreased IL-4, IL13 and IL-33 mRNA as well as IL-4, IL-5 and MIP1A protein levels in the lung tissue, suggesting decreased allergic airway sensitization. Mice sensitized in the presence of the PAR-2 blocking antibody or isotype control were then challenged intranasally with HDM extract for 4 consecutive days. Mucosal exposure to HDM extract induced AHR and airway eosinophilic inflammation. Administration of the anti-PAR-2 blocking antibody during the sensitization phase completely inhibited the development of AHR and airway inflammation in response to HDM challenge.

Conclusions

These results indicate that HDM extract induces PAR-2-dependent allergic sensitization in mice and lead to PAR-2-dependet allergic airway inflammation. These results will allow us to better define the mechanisms of allergic sensitization to allergens with serine proteinase activity.

Authors’ Affiliations

(1)
Pulmonary Research Group, Department of Medicine, University of Alberta
(2)
Department of Pharmacology and Therapeutics, University of Calgary
(3)
Immunology Research Group, University of Saskatchewan

Copyright

© Davidson et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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