Events associated with phagocytolytic activity of PMN cells

When neutrophils engulf bacteria they enclose them in small vacuoles (phagosomes) into which superoxide is released by activated NADPH oxidase (NOX2) on the internalized neutrophil membrane. The directional nature of NOX2 activity creates a charge imbalance that must be counteracted to prevent depolarization of the membrane and the shutdown of activity (Winterbourn CC et al. 2016). Also, protons are produced in the cytosol and consumed in the external compartment (for example, the phagosome) through the dismutation of superoxide. Both situations are largely overcome by a balancing flow of protons transported by voltage-gated proton channels, primarily VSOP/HV1, which are activated in parallel with the oxidase (Demaurex N & El Chemaly A 2010; El Chemaly A et al. 2010; Petheo GL et al. 2010; Kovacs I et al. 2014; Henderson LM et al. 1987, 1988). The pH of the phagosome is regulated by these activities. In contrast to the phagosomes of macrophages, in which pH drops following particle ingestion, neutrophil phagosomes remain alkaline during the period that the oxidase is active. Until recently, their pH has been accepted to lie between 7.5 and 8. However, in a 2015 study using a probe that is more sensitive at higher pH, an average pH closer to 9 was measured in individual phagosomes (Levine AP et al. 2015).<p>The superoxide dismutates to hydrogen peroxide, which is used by myeloperoxidase (MPO) to generate other oxidants, including the highly microbicidal species such as hypochlorous acid (Winterbourn CC et al. 2013, 2016).

当中性粒细胞吞噬细菌时，它们将这些细菌包围在由小囊泡（即吞噬体）所形成的结构中，吞噬体内通过被激活的NADPH氧化酶（NOX2）在内部中性粒细胞膜上释放超氧。NOX2活动的方向性产生电荷不平衡，这一不平衡必须得到抵消，以防止膜的去极化和活动性的关闭（Winterbourn CC 等人，2016年）。此外，细胞质中产生质子，并通过超氧的歧化作用在细胞外区室（例如，吞噬体）中被消耗。这两种情况在很大程度上是通过电压门控质子通道（主要为VSOP/HV1）介导的质子平衡流动来克服的，这些通道与氧化酶平行激活（Demaurex N 和 El Chemaly A，2010年；El Chemaly A 等人，2010年；Petheo GL 等人，2010年；Kovacs I 等人，2014年；Henderson LM 等人，1987年，1988年）。吞噬体的pH值由这些活动所调节。与巨噬细胞的吞噬体形成对比，巨噬细胞吞噬颗粒后pH值下降，中性粒细胞的吞噬体在氧化酶活性期间保持碱性。直到最近，它们的pH值一直被认为介于7.5到8之间。然而，在一项2015年的研究中，使用一种对较高pH值更为敏感的探针测量到单个吞噬体的平均pH值更接近9（Levine AP 等人，2015年）。超氧歧化成过氧化氢，过氧化氢被髓过氧化物酶（MPO）用于生成其他氧化剂，包括高微杀菌性的物质，如次氯酸（Winterbourn CC 等人，2013年，2016年）。