ATP-Gated P2X7 Receptors Require Chloride Channels To Promote Inflammation in Human Macrophages

Immune cells of myeloid origin show robust expression of ATP-gated P2X7 receptors, two-transmembrane ion channels permeable to Na , K , and Ca Receptor activation promotes inflammasome activation and release of the proinflammatory cytokines IL-1β and IL-18. In this study, we show that ATP generates...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2019-02, Vol.202 (3), p.883-898
Main Authors: Janks, Laura, Sprague, Randy S, Egan, Terrance M
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Adult
Aged
Animals
Cell Line
Cells, Cultured
Chloride Channels - antagonists & inhibitors
Chloride Channels - immunology
Cytokines - immunology
Female
Humans
Immunity, Innate
Inflammation
Macrophages - immunology
Male
Mice
Middle Aged
Phospholipase A2 Inhibitors
Phospholipases A2 - immunology
Receptors, Purinergic P2X1 - genetics
Receptors, Purinergic P2X4 - genetics
Receptors, Purinergic P2X7 - immunology
Signal Transduction
Young Adult
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Summary:Immune cells of myeloid origin show robust expression of ATP-gated P2X7 receptors, two-transmembrane ion channels permeable to Na , K , and Ca Receptor activation promotes inflammasome activation and release of the proinflammatory cytokines IL-1β and IL-18. In this study, we show that ATP generates facilitating cationic currents in monocyte-derived human macrophages and permeabilizes the plasma membrane to polyatomic cationic dyes. We find that antagonists of PLA and Cl channels abolish P2X7 receptor-mediated current facilitation, membrane permeabilization, blebbing, phospholipid scrambling, inflammasome activation, and IL-1β release. Our data demonstrate significant differences in the actions of ATP in murine and human macrophages and suggest that PLA and Cl channels mediate innate immunity downstream of P2X7 receptors in human macrophages.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1801101