| First Author | Karmakar M | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10555 | PubMed ID | 26877061 |
| Mgi Jnum | J:236350 | Mgi Id | MGI:5805762 |
| Doi | 10.1038/ncomms10555 | Citation | Karmakar M, et al. (2016) Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1beta secretion in response to ATP. Nat Commun 7:10555 |
| abstractText | 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-1beta 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-1beta secretion by neutrophils likely has a significant, wide ranging clinical impact. |
