NADPH Oxidase NOX2 Mediates Rapid Cellular Oxidation following ATP Stimulation of Endotoxin-Primed Macrophages
NADPH Oxidase NOX2 Mediates Rapid Cellular Oxidation following ATP Stimulation of Endotoxin-Primed Macrophages
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DOI：
10.4049/jimmunol.0900394
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发表时间：
2009-09-01
影响因子：
4.4
通讯作者：
MacKenzie, Amanda B.
中科院分区：
文献类型：
--
作者：
Moore, Samantha F.;MacKenzie, Amanda B.
吞噬细胞NADPH氧化酶（NOX 2）在宿主防御和先天免疫中起着重要作用。在这里，我们证明，外部ATP触发快速细胞氧化抑制二苯碘鎓在内毒素引发的J774巨噬细胞和原代小鼠骨髓来源的巨噬细胞。为了确定活性氧（ROS）的来源，我们比较了野生型和NOX 2缺陷型巨噬细胞之间的反应。ATP介导的ROS产生强烈衰减在NOX 2-缺陷的巨噬细胞的反应与抑制与diphenyleneiodonium。值得注意的是，观察到超氧阴离子形成的空间差异，其中ROS形成部分拮抗细胞外超氧化物歧化酶在原代骨髓来源的巨噬细胞，但不受影响的J774巨噬细胞。没有观察到NOX 2的缺失影响ATP诱导的细胞死亡。然而，ATP诱导的细胞死亡被认为是部分依赖于caspase-1和组织蛋白酶B激活。总之，NOX 2在赋予巨噬细胞对细胞外ATP刺激的反应能力中起着重要作用，细胞氧化发生了强烈的变化。免疫学杂志，2009，183：3302-3308.
The phagocytic NADPH oxidase (NOX2) plays a fundamental role in host defense and innate immunity. Here we demonstrate that external ATP triggers rapid cellular oxidation inhibited by diphenyleneiodonium in endotoxin-primed J774 macrophages and primary murine bone marrow-derived macrophages. To identify the source of reactive oxygen species (ROS), we compared responses between wild-type and NOX2-deficient macrophages. ATP-mediated ROS production was strongly attenuated in NOX2-deficient macrophages where responses were comparable to inhibition with diphenyleneiodonium. Notably, spatial differences in superoxide anion formation were observed where ROS formation was partially antagonized by extracellular superoxide dismutase in primary bone marrow-derived macrophages but unaffected in J774 macrophages. Loss of NOX2 was not observed to affect ATP-induced cell death. However, ATP-evoked cell death was found to be partially dependent on caspase-1 and cathepsin B activation. In conclusion, NOX2 plays a fundamental role in conferring macrophages with the ability to respond to extracellular ATP stimulation with robust changes in cellular oxidation. The Journal of Immunology, 2009, 183: 3302-3308.