Anding Kirsten, Gross Peter, Rost Jan M, Allgaier Dirk, Jacobs Enno
Institute of Medical Microbiology, Technical University, D-01307 Dresden, Germany.
Nephrol Dial Transplant. 2003 Oct;18(10):2067-73. doi: 10.1093/ndt/gfg330.
Neutrophil functions in haemodialysis (HD) patients are altered by uraemia and by HD procedure. We investigated details of the neutrophil dysfunction as its nature and origin is not well understood. This is reflected by conflicting results about neutrophil phagocytosis activity and by scarce data on the neutrophil killing capability in HD patients.
Using a flow-cytometric test system we have measured simultaneously phagocytosis and the production of reactive oxygen species (ROS) of neutrophils and in parallel antimicrobial killing of yeast by neutrophils. 117 whole-blood samples of healthy controls and 50 pre- and 50 post-dialysis samples of HD patients, half of them with diabetes mellitus (DM), have been evaluated. We have constructed a model to account for the dependence on the stimulus-to-cell ratio and obtain means for phagocytosis and killing at different incubation times.
(i) HD patients have significantly lower neutrophil killing (20%) than healthy controls. (ii) Dialysis improves the killing capability by 10-15%, after dialysis the killing activity remains significantly (10%) below that of the controls. (iii) The percentage of neutrophils, which exhibit phagocytosis and produce ROS, does not differ significantly between HD patients and healthy controls. (iv) Age has no significant influence on phagocytosis and killing.
The neutrophil killing capability is reduced in HD patients while the amount of neutrophils that phagocyte and produce ROS remains unchanged. Functional impairment of uraemic neutrophils is therefore mainly a result of their reduced capability to kill microorganisms intracellularly.
尿毒症及血液透析（HD）过程会改变血液透析患者中性粒细胞的功能。由于中性粒细胞功能障碍的本质和起源尚未完全明确，我们对其进行了详细研究。这一点体现在关于中性粒细胞吞噬活性的结果相互矛盾，以及血液透析患者中性粒细胞杀伤能力的数据匮乏上。
我们使用流式细胞术检测系统同时测量中性粒细胞的吞噬作用、活性氧（ROS）生成，以及中性粒细胞对酵母的抗菌杀伤作用。对117份健康对照者的全血样本以及50份血液透析患者透析前和50份透析后的样本进行了评估，其中一半患者患有糖尿病（DM）。我们构建了一个模型来解释对刺激与细胞比例的依赖性，并获得不同孵育时间下吞噬作用和杀伤作用的平均值。
（i）血液透析患者的中性粒细胞杀伤能力显著低于健康对照者（20%）。（ii）透析可使杀伤能力提高10 - 15%，透析后杀伤活性仍显著低于对照者（10%）。（iii）表现出吞噬作用并产生ROS的中性粒细胞百分比在血液透析患者和健康对照者之间无显著差异。（iv）年龄对吞噬作用和杀伤作用无显著影响。
血液透析患者中性粒细胞的杀伤能力降低，而进行吞噬作用并产生ROS的中性粒细胞数量保持不变。因此，尿毒症中性粒细胞的功能损害主要是由于其细胞内杀伤微生物的能力下降所致。
