Na+/H+ exchange and pH regulation in the control of neutrophil chemokinesis and chemotaxis
Na+/H+ exchange and pH regulation in the control of neutrophil chemokinesis and chemotaxis
复制标题
DOI：
10.1152/ajpcell.00219.2007
复制
发表时间：
2008-02-01
影响因子：
5.5
通讯作者：
Grinstein, Sergio
中科院分区：
文献类型：
--
作者：
Hayashi, Hisayoshi;Aharonovitz, Orit;Grinstein, Sergio
大的质子通量伴随着细胞迁移，但它们的确切作用仍不清楚。我们研究了pH调节过程中的趋化和趋化性在人类中性粒细胞的引诱肽刺激。化学引诱物激活细胞运动性伴随着代谢酸生成的显著增加，这归因于收缩机制的能量消耗以及NADPH氧化酶和辅助己糖单磷酸分流的刺激。尽管酸的产生增加，胞质溶胶进行了相当大的碱化，所造成的Na+/H+交换的加速。碱化的发展反映了细胞迁移速率的增加，表明存在因果关系。然而，消除Na+/H+交换省略外部Na+或通过添加有效的抑制剂是没有影响的化学运动或趋化性，提供的胞质pH值保持接近中性。在更酸性的水平下，细胞运动性逐渐受到抑制。这些观察结果表明，Na+/H+交换在细胞运动中起着允许的作用，但不需要启动或发展的迁移反应。化学运动也被发现是精致敏感的细胞外酸化。这一特性可能解释了中性粒细胞无法进入肿瘤和实体瘤的原因，据报道，这些肿瘤的pH值非常低。
Large proton fluxes accompany cell migration, but their precise role remains unclear. We studied pH regulation during the course of chemokinesis and chemotaxis in human neutrophils stimulated by attractant peptides. Activation of cell motility by chemoattractants was accompanied by a marked increase in metabolic acid generation, attributable to energy consumption by the contractile machinery and to stimulation of the NADPH oxidase and the ancillary hexose monophosphate shunt. Despite the increase in acid production, the cytosol underwent a sizable alkalinization, caused by acceleration of Na+/H+ exchange. The development of the alkalinization mirrored the increase in the rate of cell migration, suggesting a causal relationship. However, elimination of Na+/H+ exchange by omission of external Na+ or by addition of potent inhibitors was without effect on either chemokinesis or chemotaxis, provided the cytosolic pH remained near neutrality. At more acidic levels, cell motility was progressively inhibited. These observations suggest that Na+/H+ exchange plays a permissive role in cell motility but is not required for the initiation or development of the migratory response. Chemokinesis also was found to be exquisitely sensitive to extracellular acidification. This property may account for the inability of neutrophils to access abscesses and solid tumors that have been reported to have inordinately low pH.