Alkalinity of neutrophil phagocytic vacuoles is modulated by HVCN1 and has consequences for myeloperoxidase activity.
Alkalinity of neutrophil phagocytic vacuoles is modulated by HVCN1 and has consequences for myeloperoxidase activity.
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DOI：
10.1371/journal.pone.0125906
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Segal AW
中科院分区：
文献类型：
--
作者：
Levine AP;Duchen MR;de Villiers S;Rich PR;Segal AW
中性粒细胞的NADPH氧化酶是先天性免疫所必需的，它使电子穿过吞噬细胞膜，在吞噬细胞空泡中形成超氧化物。氧化酶的活性要求跨液泡膜的电荷运动是平衡的。使用pH指示剂SNARF，我们测量中性粒细胞的吞噬泡和胞质溶胶中pH的变化。在人类细胞中，空泡的pH值上升到约9，胞质溶胶轻微酸化。相比之下，在Hvcn 1敲除小鼠中性粒细胞，空泡pH值上升到11以上，空泡肿胀，胞质溶胶过度酸化，表明通常这种通道在电荷补偿中起着重要作用。质子挤出没有减少Hvcn 1-/-小鼠中性粒细胞争论其在维持跨质膜pH稳态的作用。空泡中的条件对于中性蛋白酶、组织蛋白酶G和弹性蛋白酶的细菌杀伤是最佳的，而不是髓过氧化物酶，髓过氧化物酶的活性在碱性pH下是非生理性低的。
The NADPH oxidase of neutrophils, essential for innate immunity, passes electrons across the phagocytic membrane to form superoxide in the phagocytic vacuole. Activity of the oxidase requires that charge movements across the vacuolar membrane are balanced. Using the pH indicator SNARF, we measured changes in pH in the phagocytic vacuole and cytosol of neutrophils. In human cells, the vacuolar pH rose to ~9, and the cytosol acidified slightly. By contrast, in Hvcn1 knock out mouse neutrophils, the vacuolar pH rose above 11, vacuoles swelled, and the cytosol acidified excessively, demonstrating that ordinarily this channel plays an important role in charge compensation. Proton extrusion was not diminished in Hvcn1-/- mouse neutrophils arguing against its role in maintaining pH homeostasis across the plasma membrane. Conditions in the vacuole are optimal for bacterial killing by the neutral proteases, cathepsin G and elastase, and not by myeloperoxidase, activity of which was unphysiologically low at alkaline pH.
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