Grinstein S, Swallow C J, Rotstein O D
Division of Cell Biology, Hospital for Sick Children, Toronto, Canada.
Clin Biochem. 1991 Jun;24(3):241-7. doi: 10.1016/0009-9120(91)80014-t.
To ensure effective antimicrobial or tumouricidal function, phagocytic cells must maintain their cytoplasmic pH (pHi) at a level conductive to optimal intracellular enzyme activity. The mechanisms by which neutrophils and macrophages regulate their cytoplasmic pH include bicarbonate-independent ion transport systems, most notably the Na+/H+ exchanger, and bicarbonate-dependent ion transport systems, which can be subdivided into the cation-independent and Na(+)-dependent forms of chloride/bicarbonate exchange. In addition, macrophages have been shown to recover from intracellular acid loading by means of an ATP-dependent proton extrusion mechanism, which has the characteristics of a vacuolar-type H+ ATPase. In the microenvironment typically associated with abscesses, the low extracellular pH and the presence of short chain fatty acid by-products of bacterial metabolism tend to induce cytoplasmic acid loading. In this setting, the ability of the various pHi regulatory mechanisms to protect pHi may be overcome, leading to cytoplasmic acidification. Several investigators have shown that cytoplasmic acidification impairs the ability of neutrophils to migrate in response to chemotactic stimuli, and also impairs their ability to generate a respiratory burst, thus inhibiting the release of toxic oxygen radicals. This may result in the inability of phagocytes to effect complete abscess resolution.
为确保有效的抗菌或杀肿瘤功能，吞噬细胞必须将其细胞质pH值（pHi）维持在有利于最佳细胞内酶活性的水平。中性粒细胞和巨噬细胞调节其细胞质pH值的机制包括不依赖碳酸氢盐的离子转运系统，最显著的是Na+/H+交换体，以及依赖碳酸氢盐的离子转运系统，后者可细分为不依赖阳离子和依赖Na+的氯/碳酸氢盐交换形式。此外，巨噬细胞已被证明可通过一种依赖ATP的质子外排机制从细胞内酸负荷中恢复，该机制具有液泡型H+ATP酶的特征。在通常与脓肿相关的微环境中，低细胞外pH值以及细菌代谢产生的短链脂肪酸副产物的存在往往会诱导细胞质酸负荷。在这种情况下，各种pHi调节机制保护pHi的能力可能会被克服，导致细胞质酸化。几位研究人员表明，细胞质酸化会损害中性粒细胞对趋化刺激作出迁移反应的能力，还会损害其产生呼吸爆发的能力，从而抑制有毒氧自由基的释放。这可能导致吞噬细胞无法实现脓肿的完全消退。
