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Na+/H+ exchange and pH regulation in the control of neutrophil chemokinesis and chemotaxis

机译:Na + / H +交换和pH调节控制中性粒细胞趋化和趋化性

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First published December 19, 2007; doi:10.1152/ajpcell.00219.2007.-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.
机译:首次发布于2007年12月19日; doi:10.1152 / ajpcell.00219.2007.-大质子通量伴随细胞迁移,但其确切作用尚不清楚。我们研究了由引诱剂肽刺激的人类嗜中性粒细胞在趋化和趋化过程中的pH调节。趋化因子对细胞运动的激活伴随着代谢酸生成的显着增加,这归因于收缩机制的能量消耗以及对NADPH氧化酶和辅助己糖单磷酸旁路的刺激。尽管增加了酸的产生,但由于Na + / H +交换的加速,细胞质发生了碱化反应。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。但是,通过省略外部Na +或加入强效抑制剂来消除Na + / H +交换对趋化因子或趋化性均无影响,只要细胞质的pH值保持在中性附近即可。在酸性更高的情况下,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,但对于迁移反应的启动或发展并不是必需的。还发现趋化因子对细胞外酸化非常敏感。该性质可能解释了嗜中性粒细胞无法进入脓疱和已报道的pH值过低的实体瘤。

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