Department of Neurology, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA.
Adv Exp Med Biol. 2013;961:411-8. doi: 10.1007/978-1-4614-4756-6_35.
The Na(+)/H(+) exchangers (NHEs) are a family of membrane transporter proteins which catalyze the electroneutral exchange of one Na(+) for one H(+) and thus regulate intracellular pH (pH(i)) and cell volume. It is shown that Na(+)/H(+) exchanger isoform 1 (NHE-1), but not other isoforms, is the important mechanism in extruding H(+) and regulating pH(i) in the immune system. Immune cells, such as monocytes and neutrophils, generate reactive oxygen species (ROS) and cytokines in response to various stimuli and provide the first line of defense in the immune system. NHE-1 is activated during this respiratory burst and required to maintain an optimal pH(i) for the immune cells. In the central nervous system, NHE-1 is important for microglial (macrophage) activation and participates in the inflammatory response under pathological conditions including cerebral ischemia and traumatic brain injury. NHE-1 also affects Ca(2+) homeostasis in microglia and contributes to the increase of Ca(2+) by coupling to the Na(+)/Ca(2+) exchanger (NCX) stimulation, thus regulating immune cell function and participating in ischemic cell death. A better understanding of the function of NHE-1 in inflammatory responses will provide insight into its role in brain damage under disease conditions.
钠氢交换器（NHEs）是一类膜转运蛋白，能催化 1 个钠离子与 1 个氢离子的电中性交换，从而调节细胞内 pH 值（pH(i)）和细胞体积。研究表明，钠氢交换器 1 型（NHE-1），而非其他亚型，是免疫系统中排出氢离子和调节 pH(i)的重要机制。免疫细胞（如单核细胞和中性粒细胞）在受到各种刺激后会产生活性氧（ROS）和细胞因子，并在免疫系统中提供第一道防线。在呼吸爆发过程中，NHE-1 被激活，需要维持免疫细胞的最佳 pH(i)。在中枢神经系统中，NHE-1 对于小胶质细胞（巨噬细胞）的激活很重要，并参与包括脑缺血和创伤性脑损伤在内的病理条件下的炎症反应。NHE-1 还通过与钠钙交换器（NCX）的刺激偶联影响小胶质细胞内的钙稳态，从而调节免疫细胞功能并参与缺血性细胞死亡。更好地了解 NHE-1 在炎症反应中的功能将深入了解其在疾病状态下脑损伤中的作用。
