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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >SK channels mediate NADPH oxidase-independent reactive oxygen species production and apoptosis in granulocytes
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SK channels mediate NADPH oxidase-independent reactive oxygen species production and apoptosis in granulocytes

机译：SK通道介导不依赖NADPH氧化酶的活性氧产生和粒细胞凋亡

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Neutrophils are immune cells that bind to, engulf, and destroy bacterial and fungal pathogens in infected tissue, and their clearance by apoptosis is essential for the resolution of inflammation. Killing involves both oxidative and nonoxiclative processes, the oxidative pathway requiring electrogenic production of superoxide by the membrane-bound NADPH oxidase complex. A variety of stimuli, from bacterial chemotactic peptides to complement- or IgG-opsonized microbes, can induce the production of reactive oxygen species (ROS) by neutrophils, presumably by means of NADPH oxiclase. We report here that 1-ethyl-2-benziinidazolinone (1-EBIO), an activator of Ca2+-activated potassium channels of small conductance (SK) and intermediate conductance (IK), causes production of superoxide and hydrogen peroxide by neutrophils and granulocyte-differentiated PLB-985 cells. This response can be partially inhibited by the SK blocker apamin, which inhibits a Ca2+-activated K+ current in these cells. Analysis of RNA transcripts indicates that channels encoded by the SK3 gene carry this current. The effects of 1-EBIO and apamin are independent of the NADPH oxidase pathway, as demonstrated by using a PLB-985 cell line lacking the gp91phox subunit. Rather, 1-EBIO and apamin modulate mitochondrial ROS production. Consistent with the enhanced ROS production and K+ efflux mediated by 1-EBIO, we found that this SK opener increased apoptosis of PLB-985 cells. Together, these findings suggest a previously uncharacterized mechanism for the regulation of neutrophil ROS production and programmed cell death.
机译：中性粒细胞是结合，吞噬和破坏感染组织中细菌和真菌病原体的免疫细胞，其通过凋亡的清除对于解决炎症至关重要。杀伤涉及氧化和非氧化过程，氧化途径需要通过膜结合的NADPH氧化酶复合物进行电生成超氧化物。从细菌趋化肽到补体或IgG调理过的微生物，各种各样的刺激可以诱导嗜中性粒细胞产生活性氧（ROS），大概是通过NADPH加氧酶。我们在这里报告说，1-乙基-2-苯并吲哚啉酮（1-EBIO），小电导（SK）和中电导（IK）的Ca2 +活化钾通道的活化剂，会导致中性粒细胞和粒细胞生成超氧化物和过氧化氢，分化的PLB-985细胞。 SK阻滞剂apapamin可以部分抑制这种反应，后者可以抑制这些细胞中Ca2 +激活的K +电流。 RNA转录本的分析表明，SK3基因编码的通道携带着这种电流。如使用缺少gp91phox亚基的PLB-985细胞系所证明的，1-EBIO和apamin的作用与NADPH氧化酶途径无关。而是1-EBIO和阿帕明可调节线粒体ROS的产生。与1-EBIO介导的ROS产生增加和K +外流一致，我们发现该SK开瓶剂增加了PLB-985细胞的凋亡。总之，这些发现提示了以前未知的中性粒细胞ROS产生和程序性细胞死亡的调节机制。

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