Hayashi Hisayoshi, Aharonovitz Orit, Alexander R Todd, Touret Nicolas, Furuya Wendy, Orlowski John, Grinstein Sergio
Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Physiol Cell Physiol. 2008 Feb;294(2):C526-34. doi: 10.1152/ajpcell.00219.2007. Epub 2007 Dec 19.
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.
大量质子通量伴随着细胞迁移，但其确切作用仍不清楚。我们研究了趋化运动和趋化性过程中，由趋化肽刺激的人类中性粒细胞的pH调节。趋化剂激活细胞运动伴随着代谢性产酸显著增加，这归因于收缩机制的能量消耗以及对NADPH氧化酶和辅助磷酸己糖旁路的刺激。尽管产酸增加，但由于Na(+)/H(+)交换加速，细胞质发生了相当程度的碱化。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，如果细胞质pH保持接近中性，通过省略外部Na(+)或添加强效抑制剂消除Na(+)/H(+)交换对趋化运动或趋化性均无影响。在更酸性水平下，细胞运动逐渐受到抑制。这些观察结果表明，Na(+)/H(+)交换在细胞运动中起允许作用，但对于迁移反应的启动或发展并非必需。还发现趋化运动对细胞外酸化极为敏感。这一特性可能解释了中性粒细胞无法进入据报道pH极低的脓肿和实体瘤的原因。
