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Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP
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Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP
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Journal Article
Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP
2016
Overview
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 P2X
7
R, which leads to ATP-induced loss of intracellular K
+
, NLRP3 inflammasome activation and IL-1β secretion. ATP-induced P2X
7
R activation caused a sustained increase in intracellular [Ca
2+
], which is indicative of P2X
7
R channel opening. Although there are multiple polymorphic variants of P2X
7
R, we found that neutrophils from multiple donors express P2X
7
R, but with differential efficacies in ATP-induced increase in cytosolic [Ca
2+
]. Neutrophils were also the predominant P2X
7
R-expressing cells during
Streptococcus pneumoniae
corneal infection, and P2X
7
R was required for bacterial clearance. Given the ubiquitous presence of neutrophils and extracellular ATP in multiple inflammatory conditions, ATP-induced P2X
7
R activation and IL-1β secretion by neutrophils likely has a significant, wide ranging clinical impact.
Neutrophils are a major source of IL-1 β in a number of inflammatory settings. Here the authors show that mouse and human neutrophils express functional P2X7 receptors, which mediate ATP-triggered NLRP3 inflammasome activation and IL-1 ß secretion.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 64
/ 64/110
/ 64/60
/ 96
/ Adenosine Triphosphate - immunology
/ Animals
/ Carrier Proteins - immunology
/ Enzyme-Linked Immunosorbent Assay
/ Eye Infections, Bacterial - immunology
/ Humanities and Social Sciences
/ Humans
/ Interleukin-1beta - secretion
/ Mice
/ NLR Family, Pyrin Domain-Containing 3 Protein
/ Purinergic P2X Receptor Antagonists - pharmacology
/ Receptors, Purinergic P2X7 - immunology
/ Science
