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The relationship between autophagy, increased neutrophil extracellular traps formation and endothelial dysfunction in chronic kidney disease
Clinical Immunology ( IF 4.5 ) Pub Date : 2018-10-06 , DOI: 10.1016/j.clim.2018.10.003
Jwa-Kyung Kim , Mi Jin Park , Hoi Woul Lee , Hyung Seok Lee , Sun Ryoung Choi , Young Rim Song , Hyung Jik Kim , Hyeong-Cheon Park , Sung Gyun Kim

In chronic kidney disease (CKD), the number of circulating neutrophils are increased, and this is usually accompanied by an increased basal activation state. However, the possible association between neutrophil extracellular traps (NETs) with vascular complications has not been evaluated. We assessed the relationship between NETs, autophagy and endothelial dysfunction in maintenance hemodialysis (MHD) patients. NET formation, neutrophil elastase (NE) activities, and serum nucleosome levels were measured in MHD (n = 60) and controls (n = 20). Basal NET formation were markedly increased in MHD patient compared to controls. After PMA stimulation, MHD neutrophils showed significantly increased NETs formation response than controls. The degree of NETs was strongly associated with lower flow-mediated dilatation(%) of brachial artery even after adjustment for cardiovascular risk factors and uremic toxins. Moreover, MHD neutrophils showed increased basal autophagy activity. Interestingly, the levels of NETs were markedly augmented after autophagy inhibition, suggesting a protective role of autophagy in excessive NET formation.



中文翻译:

慢性肾脏病中自噬,嗜中性粒细胞胞外陷阱形成增加与内皮功能障碍之间的关系

在慢性肾脏疾病(CKD)中,循环中性粒细胞的数量增加,这通常伴随着基础激活状态的增加。但是,尚未评估嗜中性白细胞胞外诱捕器(NETs)与血管并发症之间的可能关联。我们评估了维持性血液透析(MHD)患者中NETs,自噬与内皮功能障碍之间的关系。NET的形成,中性粒细胞弹性蛋白酶(NE)活性和血清核小体水平在MHD(n  = 60)和对照(n = 20)。与对照组相比,MHD患者的基础NET形成明显增加。在PMA刺激后,MHD中性粒细胞的NETs形成反应比对照组明显增加。即使调整了心血管危险因素和尿毒症毒素,NETs的程度也与较低的肱动脉血流介导的扩张率(%)密切相关。此外,MHD中性粒细胞显示出增加的基础自噬活性。有趣的是,自噬被抑制后,NETs的水平显着增加,表明自噬在过量NET形成中的保护作用。

更新日期:2018-10-06
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