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

Allergy Asthma and Clinical Immunology
"Decker, Inc."
Publication Date
DOI: 10.1186/1710-1492-7-s2-a30
  • Meeting Abstract
  • Biology


1710-1492-7-S2-A30 1..1 MEETING ABSTRACT 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, Harissios Vliagoftis1 From Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2011 Quebec, Canada. 20-23 October 2011 Background A number of common aeroallergens have serine protei- nase 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 air- ways leads to allergic sensitization to concomitantly inhaled antigens, implicating PAR-2 in the pathogenesis of asthma. We hypothesized that PAR-2 activation in the air- ways 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 inflamma- tion. 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 t

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