Killing activity of neutrophils is mediated through activation of proteases by K+ flux
Killing activity of neutrophils is mediated through activation of proteases by K+ flux
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DOI：
10.1038/416291a
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发表时间：
2002-03-21
期刊：
影响因子：
64.8
通讯作者：
Segal, AW
中科院分区：
文献类型：
--
作者：
Reeves, EP;Lu, H;Segal, AW
根据迄今为止接受的观点，嗜中性粒细胞通过使摄入的微生物经受高浓度的高毒性活性氧物质（ROS）并引起髓过氧化物酶催化的卤化而杀死摄入的微生物。我们在这里表明，这个简单的计划，多年来一直作为一个令人满意的工作假设，是不够的。我们发现，小鼠缺乏嗜中性粒细胞蛋白酶，但正常方面的超氧化物产生和碘化能力，是无法抵抗葡萄球菌和念珠菌感染。我们还表明，激活引起大量的ROS流入内吞泡。由此产生的阴离子电荷的积累通过以pH依赖性方式穿过膜的K+离子的激增来补偿。离子强度随之升高，导致阳离子颗粒蛋白质（包括弹性蛋白酶和组织蛋白酶G）从阴离子硫酸化蛋白聚糖基质中释放。我们表明，这是蛋白酶，从而激活，主要负责细菌的破坏。
According to the hitherto accepted view, neutrophils kill ingested microorganisms by subjecting them to high concentrations of highly toxic reactive oxygen species (ROS) and bringing about myeloperoxidase-catalysed halogenation. We show here that this simple scheme, which for many years has served as a satisfactory working hypothesis, is inadequate. We find that mice made deficient in neutrophil-granule proteases but normal in respect of superoxide production and iodinating capacity, are unable to resist staphylococcal and candidal infections. We also show that activation provokes the influx of an enormous concentration of ROS into the endocytic vacuole. The resulting accumulation of anionic charge is compensated for by a surge of K+ ions that cross the membrane in a pH-dependent manner. The consequent rise in ionic strength engenders the release of cationic granule proteins, including elastase and cathepsin G, from the anionic sulphated proteoglycan matrix. We show that it is the proteases, thus activated, that are primarily responsible for the destruction of the bacteria.