Ambient particulate matter enhances the pulmonary allergic immune response to house dust mite in a BALB/c mouse model by augmenting Th2- and Th17-immune responses.
Ambient particulate matter enhances the pulmonary allergic immune response to house dust mite in a BALB/c mouse model by augmenting Th2- and Th17-immune responses.
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DOI：
10.14814/phy2.13827
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发表时间：
2018-09
影响因子：
2.5
通讯作者：
Pinkerton KE
中科院分区：
文献类型：
--
作者：
Castañeda AR;Vogel CFA;Bein KJ;Hughes HK;Smiley-Jewell S;Pinkerton KE
环境颗粒物（PM）会加重哮喘患者的气道炎症和高反应性。研究表明，PM具有增强过敏性炎症反应的佐剂样特性；然而，PM增强这些过程的机制仍然是难以捉摸的。本研究的目的是研究环境中的PM如何增强过敏免疫反应。8周大的BALB/c小鼠被屋尘螨（HDM）或HDM和环境颗粒物（PM, 2.5 μm; Sacramento， CA）致敏，以评估PM如何调节针对过敏原的适应性免疫反应的发展。两组均仅用HDM进行挑战。支气管肺泡灌洗（BAL）检查气道炎症程度。肺组织用于组织学分析、粘膜物质定量和血红素加氧酶- 1 （HO - 1）定位/定量。在全肺中分析基因表达，以表征炎症的免疫标志物：细胞因子、趋化因子、抗氧化酶和转录因子。测定全肺细胞因子和趋化因子蛋白水平以确定基因表达模式。与仅HDM致敏相比，HDM致敏期间暴露于PM可导致气道上皮下的免疫细胞募集、IgE基因表达、粘膜物质产生和Th2相关细胞因子表达显著增加。各组间HO‐1水平无显著差异。基因表达谱表明，与仅接受HDM的小鼠相比，接受HDM和PM的小鼠中，PM中多环芳烃（PAH）含量激活了芳烃受体（AhR），并增强了Th17‐应答。研究结果表明，PM通过增强Th2介导的炎症来增强过敏致敏，PM中PAHs激活AhR可促进Th17免疫反应。
Ambient particulate matter (PM) exacerbates airway inflammation and hyper‐reactivity in asthmatic patients. Studies show that PM has adjuvant‐like properties that enhance the allergic inflammatory response; however, the mechanisms through which PM enhances these processes remain elusive. The objective of the study was to examine how ambient PM enhances the allergic immune response. Eight‐week‐old BALB/c mice were sensitized with house dust mite (HDM) or HDM and ambient particulate matter (PM, 2.5 μm; Sacramento, CA) to assess how PM modulates the development of adaptive immune responses against allergens. Both groups were challenged with HDM only. Bronchoalveolar lavage (BAL) was analyzed for extent of airway inflammation. Lung tissue was used for histological analysis, mucosubstance quantification, and heme oxygenase‐1 (HO‐1) localization/quantification. Gene expression was analyzed in whole lung to characterize immune markers of inflammation: cytokines, chemokines, antioxidant enzymes, and transcription factors. Cytokine and chemokine protein levels were quantified in whole lung to confirm gene expression patterns. Compared to HDM‐only sensitization, exposure to PM during HDM sensitization led to significant immune cell recruitment into the airway subepithelium, IgE gene expression, mucosubstance production, and Th2‐associated cytokine expression. HO‐1 levels were not significantly different between the treatment groups. Gene expression profiles suggest that polycyclic aromatic hydrocarbon (PAH) content in PM activated the aryl hydrocarbon receptor (AhR) and enhanced Th17‐responses in the mice that received HDM and PM compared to mice that received HDM‐only. The findings suggest that PM enhances allergic sensitization via enhancement of Th2‐mediated inflammation and that AhR activation by PAHs in PM promotes Th17‐immune responses.