Murphy Ricardo, DeCoursey Thomas E
Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL 60612, USA.
Biochim Biophys Acta. 2006 Aug;1757(8):996-1011. doi: 10.1016/j.bbabio.2006.01.005. Epub 2006 Jan 30.
The phagocyte NADPH oxidase produces superoxide anion (O(2)(.-)) by the electrogenic process of moving electrons across the cell membrane. This charge translocation must be compensated to prevent self-inhibition by extreme membrane depolarization. Examination of the mechanisms of charge compensation reveals that these mechanisms perform several other vital functions beyond simply supporting oxidase activity. Voltage-gated proton channels compensate most of the charge translocated by the phagocyte NADPH oxidase in human neutrophils and eosinophils. Quantitative modeling of NADPH oxidase in the plasma membrane supports this conclusion and shows that if any other conductance is present, it must be miniscule. In addition to charge compensation, proton flux from the cytoplasm into the phagosome (a) helps prevent large pH excursions both in the cytoplasm and in the phagosome, (b) minimizes osmotic disturbances, and (c) provides essential substrate protons for the conversion of O(2)(*-) to H(2)O(2) and then to HOCl. A small contribution by K+ or Cl- fluxes may offset the acidity of granule contents to keep the phagosome pH near neutral, facilitating release of bactericidal enzymes. In summary, the mechanisms used by phagocytes for charge compensation during the respiratory burst would still be essential to phagocyte function, even if NADPH oxidase were not electrogenic.
吞噬细胞NADPH氧化酶通过将电子跨细胞膜转运的产电过程产生超氧阴离子（O₂⁻·）。这种电荷转运必须得到补偿，以防止因极端的膜去极化而产生自我抑制。对电荷补偿机制的研究表明，这些机制除了简单地支持氧化酶活性外，还执行其他几种重要功能。电压门控质子通道补偿了人类中性粒细胞和嗜酸性粒细胞中吞噬细胞NADPH氧化酶转运的大部分电荷。质膜中NADPH氧化酶的定量模型支持这一结论，并表明如果存在任何其他电导，其必定极小。除电荷补偿外，质子从细胞质流入吞噬体：（a）有助于防止细胞质和吞噬体中的pH值大幅波动；（b）使渗透干扰最小化；（c）为O₂⁻·转化为H₂O₂进而转化为HOCl提供必需的底物质子。K⁺或Cl⁻通量的微小贡献可能会抵消颗粒内容物的酸度，使吞噬体pH值保持接近中性，从而促进杀菌酶的释放。总之，即使NADPH氧化酶不产生电，吞噬细胞在呼吸爆发期间用于电荷补偿的机制对吞噬细胞功能仍然至关重要。
