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Innate Immun. 2014 Aug;20(6):618-25. doi: 10.1177/1753425913503387. Epub 2013 Sep 18.

Protease-activated receptor-2 deficient mice have reduced house dust mite-evoked allergic lung inflammation.

Author information

1
Academic Medical Center, University of Amsterdam, Center of Infection and Immunity Amsterdam & Center for Experimental and Molecular Medicine, Amsterdam, the Netherlands j.d.deboer@amc.uva.nl.
2
Academic Medical Center, University of Amsterdam, Center of Infection and Immunity Amsterdam & Center for Experimental and Molecular Medicine, Amsterdam, the Netherlands.
3
Academic Medical Center, University of Amsterdam, Center of Infection and Immunity Amsterdam & Center for Experimental and Molecular Medicine, Amsterdam, the Netherlands Department of Immunopathology, Sanquin, Amsterdam, the Netherlands.
4
Department of Pulmonology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.
5
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
6
Academic Medical Center, University of Amsterdam, Center of Infection and Immunity Amsterdam & Center for Experimental and Molecular Medicine, Amsterdam, the Netherlands Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Abstract

Protease-activated receptor-2 (PAR2) is abundantly expressed in the pulmonary compartment. House dust mite (HDM) is a common cause of allergic asthma and contains multiple PAR2 agonistic proteases. The aim of this study was to determine the role of PAR2 in HDM-induced allergic lung inflammation. For this, the extent of allergic lung inflammation was studied in wild type (Wt) and PAR2 knockout (KO) mice after repeated airway exposure to HDM. HDM exposure of Wt mice resulted in a profound influx of eosinophils in bronchoalveolar lavage fluid (BALF) and accumulation of eosinophils in lung tissue, which both were strongly reduced in PAR2 KO mice. PAR2 KO mice demonstrated attenuated lung pathology and protein leak in the bronchoalveolar space, accompanied by lower BALF levels of the anaphylatoxins C3a and C5a. This study reveals, for the first time, an important role for PAR2 in allergic lung inflammation induced by the clinically relevant allergens contained in HDM.

KEYWORDS:

Asthma; allergic lung inflammation; house dust mite; protease-activated receptor-2

PMID:
24048772
DOI:
10.1177/1753425913503387
[Indexed for MEDLINE]

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