The role of protease-activated receptor-2 on pulmonary neutrophils in the innate immune response to cockroach allergenReportar como inadecuado

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Journal of Inflammation

, 9:32

First Online: 06 September 2012Received: 04 May 2012Accepted: 23 August 2012


BackgroundSerine proteases in German cockroach GC have been shown to mediate allergic airway inflammation through the activation of protease activated receptor PAR-2. Neutrophils play an important role in regulating the innate immune response, and are recruited into the airways following GC frass exposure. As such, we investigated the role of PAR-2 in airway neutrophil recruitment, activation and cytokine production following allergen exposure.

MethodsWild type and PAR-2-deficient mice were administered a single intratracheal instillation of PBS or GC frass and neutrophil recruitment, expression of PAR-2, CD80, CD86, and MHC class II were assessed by flow cytometry and levels of tumor necrosis factor TNFα was assessed by ELISA. Uptake of AlexaFluor 405-labeled GC frass by neutrophils was performed by flow cytometry.

ResultsNeutrophil recruitment in the lung and airways following GC frass exposure was significantly decreased in PAR-2-deficient mice compared to wild type mice. GC frass exposure increased the level of PAR-2 on pulmonary neutrophils and increased numbers of PAR-2-positive neutrophils were found in the lungs; however PAR-2 did not play a role in meditating allergen uptake. Comparing wild type and PAR-2-deficient mice, we found that a single exposure to GC frass increased levels of CD80 and CD86 on pulmonary neutrophils, an effect which was independent of PAR-2 expression. Neutrophils isolated from the whole lungs of naïve PAR-2-deficient mice treated ex vivo with GC frass produced significantly less TNFα than in similarly treated wild type neutrophils. Lastly, neutrophils were isolated from the bronchoalveolar lavage fluid of wild type and PAR-2-deficient mice following a single intratracheal exposure to GC frass. Airway neutrophils from PAR-2-deficient mice released substantially decreased levels of TNFα, suggesting a role for PAR-2 in neutrophil-derived cytokine production.

ConclusionsTogether these data suggest PAR-2 expression can be upregulated on lung neutrophils following allergen exposure and the consequence is altered release of TNFα which could drive the early innate immune response.

AbbreviationsAFAlexa Fluor

BALBronchoalveolar lavage

CDCluster of differentiation

GCGerman cockroach

MFIMean fluorescence intensity

MHCMajor histocompatibility complex

NF-κBNuclear factor κB

PARProtease activated receptor

TNFTumor necrosis factor.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-9255-9-32 contains supplementary material, which is available to authorized users.

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Autor: Riad Lutfi - Ian P Lewkowich - Ping Zhou - John R Ledford - Kristen Page


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