ATP-Gated P2X7 Receptors Require Chloride Channels To Promote Inflammation in Human Macrophages
ATP-Gated P2X7 Receptors Require Chloride Channels To Promote Inflammation in Human Macrophages
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DOI：
10.4049/jimmunol.1801101
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发表时间：
2019-02-01
影响因子：
4.4
通讯作者：
Egan, Terrance M.
中科院分区：
文献类型：
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作者：
Janks, Laura;Sprague, Randy S.;Egan, Terrance M.
骨髓来源的免疫细胞显示出 ATP 门控 P2X7 受体、可渗透 Na+、K+ 和 Ca2+ 的两次跨膜离子通道的强烈表达。受体激活促进炎症小体激活并释放促炎细胞因子 IL-1β 和 IL-18。在这项研究中，我们发现 ATP 在单核细胞衍生的人类巨噬细胞中产生促进阳离子电流，并使质膜渗透到多原子阳离子染料中。我们发现 PLA(2) 和 Cl-通道的拮抗剂消除了 P2X7 受体介导的电流促进、膜通透、起泡、磷脂扰乱、炎症小体激活和 IL-1 β 释放。我们的数据表明，小鼠和人类巨噬细胞中 ATP 的作用存在显着差异，并表明 PLA(2) 和 Cl-通道介导人类巨噬细胞中 P2X7 受体下游的先天免疫。
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 beta 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(2) and Cl- channels abolish P2X7 receptor-mediated current facilitation, membrane permeabilization, blebbing, phospholipid scrambling, inflammasome activation, and IL-1 beta release. Our data demonstrate significant differences in the actions of ATP in murine and human macrophages and suggest that PLA(2) and Cl- channels mediate innate immunity downstream of P2X7 receptors in human macrophages.