Swallow C J, Grinstein S, Sudsbury R A, Rotstein O D
Department of Surgery, Toronto Hospital, Ontario.
Clin Invest Med. 1991 Oct;14(5):367-78.
Maintenance of cytoplasmic pH (pHi) within a narrow physiological range is critical to optimal cell function. Monocytes and macrophages (Møs) actively regulate their pHi through three distinct plasma membrane ion transport systems: (1) Na+/H+ exchange; (2) Na(+)-dependent anion exchange; and (3) vacuolar-type H+ ATPases. Alterations in the functional state of monocytes and Møs have been linked to changes in pHi and/or its regulation by these ion transport systems. Differentiation, proliferation, and activation of Møs in response to a variety of agents are associated with increased Na+/H+ exchange. The resultant cytoplasmic alkalinization typically observed in HCO3(-)-free media likely plays a permissive, rather than a triggering, role in mediating Mø response to most of these agents. Prevention of cytoplasmic acidification is essential during Mø activation, when production of metabolic acid increases. This is of particular importance within the in vivo microenvironment of an abscess or tumour, where pHi is further threatened by the low extracellular pH (pHo) which typically prevails. At low pHo, H+ ATPase-mediated H+ extrusion plays a critical role in maintenance of pHi, preserving the ability of Møs to generate a respiratory burst. The requirement for maintenance of pHi within a range conducive to efficient Mø function may explain why Møs have acquired a variety of parallel systems for pHi regulation.
将细胞质pH（pHi）维持在狭窄的生理范围内对细胞的最佳功能至关重要。单核细胞和巨噬细胞（Mø）通过三种不同的质膜离子转运系统积极调节其pHi：（1）Na⁺/H⁺交换；（2）Na⁺依赖性阴离子交换；以及（3）液泡型H⁺ATP酶。单核细胞和Mø功能状态的改变与pHi及其通过这些离子转运系统的调节变化有关。Mø对多种因子的分化、增殖和激活与Na⁺/H⁺交换增加有关。在无HCO₃⁻的培养基中通常观察到的细胞质碱化在介导Mø对大多数这些因子的反应中可能起允许作用，而非触发作用。在Mø激活期间，当代谢酸产生增加时，防止细胞质酸化至关重要。这在脓肿或肿瘤的体内微环境中尤为重要，在那里pHi受到普遍存在的低细胞外pH（pHo）的进一步威胁。在低pHo时，H⁺ATP酶介导的H⁺外排在维持pHi方面起关键作用，保持Mø产生呼吸爆发的能力。在有利于Mø有效功能的范围内维持pHi的需求可能解释了为什么Mø获得了多种并行的pHi调节系统。
