Department of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
Department of Medical Genetics, The Third Military Medical University, Chongqing 400038, China.
J Immunol Res. 2017;2017:5358647. doi: 10.1155/2017/5358647. Epub 2017 May 25.
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.
三磷酸腺苷（ATP）通过作用于 P2 受体，成为提示免疫功能障碍的关键介质。在此，我们发现变应原刺激会引起中性粒细胞性哮喘小鼠模型中 ATP 的分泌增加，这与中性粒细胞计数和白细胞介素-17 的产生密切相关。在刺激前通过气管内给予 ATP 受体拮抗剂苏拉明阻断 ATP 信号，可显著减少中性粒细胞性气道炎症、气道高反应性和 Th17 型反应。另外，使用 apyrase 局部中和气道中的 ATP 水平可消除中性粒细胞炎症。此外，ATP 可促进来自 DO11.10 小鼠的脾 CD4 T 细胞向 Th17 极化。此外，卵清蛋白（OVA）刺激可在 DO11.10 小鼠中诱导中性粒细胞炎症和 Th17 极化，而在刺激前给予苏拉明可减轻这些参数。因此，ATP 可能是中性粒细胞性哮喘的标志物，局部阻断 ATP 信号可能为预防中性粒细胞性哮喘中的 Th17 介导的气道炎症提供一种替代方法。
