Protease-activated receptor-2 deficient mice have reduced house dust mite-evoked allergic lung inflammation.
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.
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.
J Daan
JD
de Boer
Academic Medical Center, University of Amsterdam, Center of Infection and Immunity Amsterdam & Center for Experimental and Molecular Medicine, Amsterdam, the Netherlands.
Cornelis
C
Van't Veer
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.
Ingrid
I
Stroo
Academic Medical Center, University of Amsterdam, Center of Infection and Immunity Amsterdam & Center for Experimental and Molecular Medicine, Amsterdam, the Netherlands.
Anne J
AJ
van der Meer
Academic Medical Center, University of Amsterdam, Center of Infection and Immunity Amsterdam & Center for Experimental and Molecular Medicine, Amsterdam, the Netherlands.
Alex F
AF
de Vos
Department of Pulmonology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.
Jaring S
JS
van der Zee
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Joris J T H
JJ
Roelofs
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.
Tom
T
van der Poll
D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid; D015926:Complement C3a / Q000235:genetics / Q000276:immunology; D015936:Complement C5a / Q000235:genetics / Q000276:immunology; D040001:Dermatophagoides farinae / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D044464:Receptor, PAR-2 / Q000172:deficiency* / Q000235:genetics*
D044464:Receptor, PAR-2; D015926:Complement C3a; D015936:Complement C5a
Asthma; allergic lung inflammation; house dust mite; protease-activated receptor-2