Superoxide production by phagocytosing macrophages in relation to the intracellular distribution of oxygen
Superoxide production by phagocytosing macrophages in relation to the intracellular distribution of oxygen
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DOI：
10.1002/jlb.64.1.78
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发表时间：
1998-07-01
影响因子：
5.5
通讯作者：
Swartz, HM
中科院分区：
文献类型：
--
作者：
James, PE;Grinberg, OY;Swartz, HM
我们同时测量了巨噬细胞吞噬体和细胞外区室中的氧气 ([O-2]) 浓度。通过将电子顺磁共振 (EPR) 血氧测定技术与自旋捕获技术相结合，我们发现这两个区室之间存在显着的氧浓度 ([O-2]) 差异，并且我们能够监测 (1) 细胞外区室中的 [O-2] 和线粒体消耗速率如何影响 [O-2] 的这种差异，以及 (2) [O-2] 的这种梯度在多大程度上影响吞噬体产生活性氧。流入气体中的[O-2]较高（210μM；空气），细胞外室和吞噬体室中的[O-2]分别为180μM和141μM。这足以维持这些细胞中最大的超氧化物产量。当细胞外 [O-2] 降低至 84 或 36 μM 时，细胞内吞噬体中的 [O-2]（分别为 31.7 和 7.7 μM）太低，无法维持吞噬体内 NADPH 氧化酶系统产生的超氧化物，然而，这些样品的细胞外区室中的 [Oz] 始终足以维持细胞表面吞噬体产生的超氧化物。我们的研究结果表明，巨噬细胞周围和内部的氧气分布可以影响其执行杀菌和杀肿瘤功能的能力，即使在介质中的 [O-2] 似乎足够的情况下也是如此。
We simultaneously measured the concentration of oxygen ([O-2]) within the phagosomal and extracellular compartments of macrophages. By combining electron paramagnetic resonance (EPR) oximetry techniques with that of spin-trapping, we found that a significant difference in oxygen concentration ([O-2]) exists between these two compartments and we were able to monitor (1) how [O-2] in the extracellular compartment and the rate of mitochondrial consumption affected this difference in [O-2], and (2) to what extent this gradient of [O-2] influenced production of reactive oxygen species by phagosomes, Under conditions where the [O-2] in the inflowing gas was high (210 mu M; air), the [O-2] in the extracellular and phagosomal compartments was 180 and 141 mu M, respectively. This was sufficient to maintain maximum superoxide production in these cells. When extracellular [O-2] was reduced to 84 or 36 mu M the [O-2] in phagosomes within the cells (31.7 and 7.7 mu M, respectively) was too low to maintain superoxide production by the NADPH-oxidase system within the phagosomes, The[Oz] in the extracellular compartments of these samples, however, was always sufficient to maintain superoxide production by phagosomes at the cell surface. Our findings suggest that the distribution of oxygen surrounding and within macrophages can influence their ability to perform microbicidal and tumoricidal functions, even at an [O-2] in the media that appears to be adequate.