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

ABSTRACT: Immune cells of myeloid origin show robust expression of ATP-gated P2X7 receptors, two-transmembrane ion channels permeable to Na+, K+, and Ca2+ Receptor activation promotes inflammasome activation and release of the proinflammatory cytokines IL-1? 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 PLA2 and Cl- channels abolish P2X7 receptor-mediated current facilitation, membrane permeabilization, blebbing, phospholipid scrambling, inflammasome activation, and IL-1? release. Our data demonstrate significant differences in the actions of ATP in murine and human macrophages and suggest that PLA2 and Cl- channels mediate innate immunity downstream of P2X7 receptors in human macrophages.

SUBMITTER: Janks L

PROVIDER: S-EPMC6352910 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Janks Laura L Sprague Randy S RS Egan Terrance M TM

Journal of immunology (Baltimore, Md. : 1950) 20181231 3

Immune cells of myeloid origin show robust expression of ATP-gated P2X7 receptors, two-transmembrane ion channels permeable to Na+, K+, and Ca2+ 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 P ...[more]

PMID: 30598517

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