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J Immunol. 2019 Feb 1;202(3):883-898. doi: 10.4049/jimmunol.1801101. Epub 2018 Dec 31.

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

Author information

1
Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO 63104.
2
Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO 63104 terrance.egan@health.slu.edu.

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-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 PLA2 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 PLA2 and Cl- channels mediate innate immunity downstream of P2X7 receptors in human macrophages.

PMID:
30598517
PMCID:
PMC6352910
[Available on 2020-02-01]
DOI:
10.4049/jimmunol.1801101
[Indexed for MEDLINE]

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