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

Journal of Inflammation

Research

Riad Lutfi¹  Ping Zhou¹  John R Ledford¹  Kristen Page²  Ian P Lewkowich³ 

[1] Department of Pediatrics, Division of Critical Care Medicine, Cincinnati, OH, USA;Department of Pediatrics, Division of Critical Care Medicine, Cincinnati, OH, USA;Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;

关键词: Neutrophil Recruitment;    Allergen Exposure;    Extracellular Regulate Kinase;    Allergic Airway Inflammation;    German Cockroach;   

DOI  :  10.1186/1476-9255-9-32

 received in 2012-05-04, accepted in 2012-08-23,  发布年份 2012

来源: Springer

【 摘 要 】

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 (TNF)α 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.

【 授权许可】

Unknown   
© Lutfi et al.; licensee BioMed Central Ltd. 2012. 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.