Although extracellular ATP is abundant at sites of inflammation, its role in activating inflammasome signalling in neutrophils is not well characterized. In the current study, we demonstrate that human and murine neutrophils express functional cell-surface P2X7R, which leads to ATP-induced loss of intracellular K(+), NLRP3 inflammasome activation and IL-1β secretion. ATP-induced P2X7R activation caused a sustained increase in intracellular [Ca(2+)], which is indicative of P2X7R channel opening. Although there are multiple polymorphic variants of P2X7R, we found that neutrophils from multiple donors express P2X7R, but with differential efficacies in ATP-induced increase in cytosolic [Ca(2+)]. Neutrophils were also the predominant P2X7R-expressing cells during Streptococcus pneumoniae corneal infection, and P2X7R was required for bacterial clearance. Given the ubiquitous presence of neutrophils and extracellular ATP in multiple inflammatory conditions, ATP-induced P2X7R activation and IL-1β secretion by neutrophils likely has a significant, wide ranging clinical impact.

中文翻译：

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中性粒细胞P2X7受体响应ATP介导NLRP3炎性小体依赖性IL-1β分泌。

尽管细胞外ATP在炎症部位丰富，但其在嗜中性粒细胞中激活炎性体信号传导的作用尚不十分清楚。在当前的研究中，我们证明人和鼠中性粒细胞表达功能性细胞表面P2X7R，这导致ATP诱导的细胞内K（+）丢失，NLRP3炎性小体活化和IL-1β分泌。ATP诱导的P2X7R激活引起细胞内[Ca（2+）]的持续增加，这表明P2X7R通道打开。虽然有P2X7R的多个多态性变体，但我们发现来自多个供体的中性粒细胞表达P2X7R，但在ATP诱导的胞质[Ca（2+）]增加中具有不同的功效。中性粒细胞也是肺炎链球菌角膜感染期间主要表达P2X7R的细胞，细菌清除需要P2X7R。