During the respiratory burst, do phagocytes need proton channels or potassium channels, or both?
During the respiratory burst, do phagocytes need proton channels or potassium channels, or both?
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DOI：
10.1126/stke.2332004pe21
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发表时间：
2004-05-11
期刊：
影响因子：
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通讯作者：
DeCoursey, Thomas E
中科院分区：
文献类型：
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作者：
DeCoursey, Thomas E
NADPH（还原型烟酰胺腺嘌呤二核苷酸磷酸）氧化酶复合物是先天免疫的关键组分，产生超氧阴离子（O2-），其是许多活性氧的前体。NADPH氧化酶通过将电子从细胞内NADPH跨膜转移到细胞外（或吞噬体）氧来产生O2-，因此是产电的。人们普遍认为，电中性是由通过电压门控质子通道的质子通量保持的。最近的一系列论文对这种“呼吸爆发”观点的几个关键方面提出了质疑。“最近的研究巩固了吞噬细胞产生的O2-和其他活性氧物质在生理条件下对微生物无毒的提议。此外，高电导，Ca 2+激活的K+（maxi-K+）通道在微生物杀灭中的重要作用。最后，结果对广泛持有的观点提出了质疑，即H+通过电压门控质子通道流出（i）是电荷补偿的主要机制，（ii）是NADPH氧化酶连续产生O2的必要条件。我对新数据和文献中大量数据的分析表明，最大钾离子通道在呼吸爆发中的作用尚未完全确立。因此，通过质子通道的H+流出仍然是电荷补偿和连续O2-生产的最可行的机制。活性氧在吞噬细胞和其他细胞中的毒性这一重要问题，长期以来一直被认为是理所当然的，是一个值得批判性研究的普遍假设。
The NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase enzyme complex, a crucial component of innate immunity, produces superoxide anion (O2-), which is a precursor to many reactive oxygen species. NADPH oxidase produces O2- by transferring electrons from intracellular NADPH across the membrane to extracellular (or phagosomal) oxygen and is thus electrogenic. It is widely believed that electroneutrality is preserved by proton flux through voltage-gated proton channels. A series of recent papers have challenged several key aspects of this view of the "respiratory burst." The most recent study solidifies the proposal that O2- and other reactive oxygen species produced by phagocytes are not toxic to microbes under physiological conditions. Further, an essential role for high-conductance, Ca2+-activated K+ (maxi-K+) channels in microbe killing is proposed. Finally, the results cast doubt on the widely held view that H+ efflux through voltage-gated proton channels (i) is the main mechanism of charge compensation, and (ii) is essential to continuous O2- production by the NADPH oxidase. My analysis of the new data and of a large body of data in the literature indicates that the proposed role of maxi-K+ channels in the respiratory burst is not yet credibly established. H+ efflux through proton channels thus remains the most viable mechanism for charge compensation and continuous O2- production. The important question of the toxicity of reactive oxygen species in phagocytes and in other cells, which has long been simply taken for granted, is a widespread assumption that deserves critical study.