Adenosine Triphosphate Promotes Allergen-Induced Airway Inflammation and Th17 Cell Polarization in Neutrophilic Asthma.
Adenosine Triphosphate Promotes Allergen-Induced Airway Inflammation and Th17 Cell Polarization in Neutrophilic Asthma.
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三磷酸腺苷促进中性粒细胞性哮喘中过敏原诱导的气道炎症和 Th17 细胞极化
DOI：
10.1155/2017/5358647
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发表时间：
2017
影响因子：
4.1
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Zhang F;Su X;Huang G;Xin XF;Cao EH;Shi Y;Song Y
三磷酸腺苷（ATP）是通过作用于P2受体来提醒免疫功能障碍的关键介体。在这里，我们发现过敏原挑战在嗜中性粒细胞性哮喘的鼠模型中引起了ATP分泌的增加，这与中性粒细胞计数和白介素17的产生很好地相关。当挑战前ATP受体拮抗剂苏拉蛋白的气管内施用ATP信号传导时，中性粒细胞气道炎症，气道高反应性和Th17型反应显着降低。同样，当使用Apyrase局部对气道ATP水平进行局部中和时，中性粒细胞炎症被废除。此外，ATP在体外促进了来自DO11.10小鼠的脾脏CD4+ T细胞的Th17极化。此外，卵蛋白（OVA）挑战在DO11.10小鼠中诱导嗜中性炎症和Th17极化，而在挑战之前施用苏拉蛋白可以缓解这些参数。因此，ATP可以用作嗜中性哮喘的标志物，而局部对ATP信号的阻塞可能会提供一种替代方法，以防止Th17介导的嗜中性粒细胞性哮喘中的气道炎症。
Adenosine triphosphate (ATP) is a key mediator to alert the immune dysfunction by acting on P2 receptors. Here, we found that allergen challenge caused an increase of ATP secretion in a murine model of neutrophilic asthma, which correlated well with neutrophil counts and interleukin-17 production. When ATP signaling was blocked by intratracheal administration of the ATP receptor antagonist suramin before challenge, neutrophilic airway inflammation, airway hyperresponsiveness, and Th17-type responses were reduced significantly. Also, neutrophilic inflammation was abrogated when airway ATP levels were locally neutralized using apyrase. Furthermore, ATP promoted the Th17 polarization of splenic CD4+ T cells from DO11.10 mice in vitro. In addition, ovalbumin (OVA) challenge induced neutrophilic inflammation and Th17 polarization in DO11.10 mice, whereas administration of suramin before challenge alleviated these parameters. Thus, ATP may serve as a marker of neutrophilic asthma, and local blockade of ATP signaling might provide an alternative method to prevent Th17-mediated airway inflammation in neutrophilic asthma.