Hv1 proton channels are required for high-level NADPH oxidase-dependent superoxide production during the phagocyte respiratory burst
Hv1 proton channels are required for high-level NADPH oxidase-dependent superoxide production during the phagocyte respiratory burst
复制标题
DOI：
10.1073/pnas.0902761106
复制
发表时间：
2009-05-05
影响因子：
11.1
通讯作者：
Clapham, David E.
中科院分区：
文献类型：
--
作者：
Ramsey, I. Scott;Ruchti, Evelyne;Clapham, David E.
粒细胞产生NADPH氧化酶依赖性超氧阴离子（O-2（-中心点））产生的“呼吸爆发”，这是有效清除细菌病原体所必需的。Hv 1介导电压门控H+通道活性，其被提议在粒细胞吞噬细胞如中性粒细胞和嗜酸性粒细胞中起电荷平衡作用。使用小鼠，其中编码Hv 1的基因被β-Geo报告蛋白序列所取代，我们表明，Hv 1的表达所需的可测量的电压门控H+电流在未受刺激的吞噬细胞。O-2（-中心点）生产大幅减少，在没有Hv 1，这表明Hv 1贡献了最佳NADPH氧化酶活性所需的大部分电荷补偿。尽管超氧化物产生显著减少，但Hv 1（-/-）小鼠能够清除几种类型的细菌感染。
Granulocytes generate a "respiratory burst'' of NADPH oxidase-dependent superoxide anion (O-2(-center dot)) production that is required for efficient clearance of bacterial pathogens. Hv1 mediates a voltage-gated H+ channel activity that is proposed to serve a charge-balancing role in granulocytic phagocytes such as neutrophils and eosinophils. Using mice in which the gene encoding Hv1 is replaced by beta-Geo reporter protein sequence, we show that Hv1 expression is required for measurable voltage-gated H+ current in unstimulated phagocytes. O-2(-center dot) production is substantially reduced in the absence of Hv1, suggesting that Hv1 contributes a majority of the charge compensation required for optimal NADPH oxidase activity. Despite significant reduction in superoxide production, Hv1(-/-) mice are able to clear several types of bacterial infections.