Department of Nephrology and Dialysis, Medical University of Vienna, Vienna A-1090, Austria.
School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Toxins (Basel). 2019 Feb 1;11(2):73. doi: 10.3390/toxins11020073.
The anti-inflammatory properties of high-density lipoproteins (HDL) are lost in uremia. These HDL may show pro-inflammatory features partially as a result of changed protein composition. Alterations of polymorphonuclear leukocytes (PMNLs) in chronic kidney disease (CKD) may contribute to chronic inflammation and high vascular risk. We investigated if HDL from uremic patients is related to systemic inflammation by interfering with PMNL function. PMNL apoptosis was investigated by assessing morphological features and DNA content. CD11b surface expression was quantified by flow cytometry. Oxidative burst was measured via cytochrome c reduction assay. Chemotaxis was assessed by using an under-agarose migration assay. We found that HDL from CKD and hemodialysis (HD) patients significantly attenuated PMNL apoptosis, whereas HDL isolated from healthy subjects had no effect on PMNL apoptosis. The use of signal transduction inhibitors indicated that uremic HDL exerts anti-apoptotic effects by activating pathways involving phosphoinositide 3-kinase and extracellular-signal regulated kinase. Healthy HDL attenuated the surface expression of CD11b, whereas HDL from CKD and HD patients had no effect. All tested isolates increased the stimulation of oxidative burst, but did not affect PMNL chemotactic movement. In conclusion, HDL may contribute to the systemic inflammation in uremic patients by modulating PMNL functions.
高密度脂蛋白（HDL）的抗炎特性在尿毒症中丧失。这些 HDL 可能表现出促炎特征，部分原因是蛋白质组成发生了变化。慢性肾脏病（CKD）中的多形核白细胞（PMNL）的改变可能导致慢性炎症和高血管风险。我们研究了尿毒症患者的 HDL 是否通过干扰 PMNL 功能与全身炎症有关。通过评估形态特征和 DNA 含量来研究 PMNL 凋亡。通过流式细胞术定量测定 CD11b 表面表达。通过细胞色素 c 还原测定法测量氧化爆发。通过琼脂糖下迁移测定评估趋化性。我们发现 CKD 和血液透析（HD）患者的 HDL 显著减弱了 PMNL 凋亡，而来自健康受试者的 HDL 对 PMNL 凋亡没有影响。使用信号转导抑制剂表明，尿毒症 HDL 通过激活涉及磷酸肌醇 3-激酶和细胞外信号调节激酶的途径发挥抗凋亡作用。健康的 HDL 减弱了 CD11b 的表面表达，而 CKD 和 HD 患者的 HDL 则没有影响。所有测试的分离物均增加了氧化爆发的刺激，但不影响 PMNL 趋化运动。总之，HDL 可能通过调节 PMNL 功能导致尿毒症患者的全身炎症。
