The influence of uraemia and haemodialysis on neutrophil phagocytosis and antimicrobial killing

The influence of uraemia and haemodialysis on neutrophil phagocytosis and antimicrobial killing
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DOI:
10.1093/ndt/gfg330
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发表时间:
2003-10-01
影响因子:
6.1
通讯作者:
Jacobs, E
Jacobs, E
中科院分区:
医学1区
文献类型:
--
作者:
Anding, K;Gross, P;Jacobs, E

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背景血液透析(HD)患者的神经功能会因尿毒症和HD手术而改变。我们研究了中性粒细胞功能障碍的细节,因为其性质和起源还不清楚。这反映在关于中性粒细胞吞噬活性的相互矛盾的结果和关于HD患者中性粒细胞杀伤能力的缺乏数据上。使用流式细胞术检测系统,我们已经同时测量吞噬作用和中性粒细胞的活性氧(ROS)的产生,并在平行的抗菌杀死酵母的中性粒细胞。对117份健康对照的全血样本和50份透析前和50份透析后HD患者样本(其中一半患有糖尿病(DM))进行了评价。我们已经构建了一个模型来解释刺激与细胞比率的依赖性,并获得了在不同孵育时间下的吞噬和杀伤手段。(i)HD患者的中性粒细胞杀伤(20%)显著低于健康对照。(ii)透析提高了10- 15%的杀伤能力,透析后的杀伤活性仍显着(10%)低于对照。(iii)表现出吞噬作用并产生ROS的中性粒细胞的百分比。在HD患者和健康对照之间没有显著差异。(iv)年龄对吞噬和吞噬功能无明显影响。HD患者的中性粒细胞杀伤能力降低,而吞噬和产生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其细胞内杀死微生物的能力降低的结果。
Background. 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.Methods. 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.Results. (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.Conclusion. 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.