Effects of end-stage renal disease and haemodialysis on dendritic cell subsets and basal and LPS-stimulated cytokine production
Effects of end-stage renal disease and haemodialysis on dendritic cell subsets and basal and LPS-stimulated cytokine production
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DOI：
10.1093/ndt/gfp580
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发表时间：
2010-03-01
影响因子：
6.1
通讯作者：
Vaziri, Nosratola D.
中科院分区：
文献类型：
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作者：
Agrawal, Sudhanshu;Gollapudi, Pavan;Vaziri, Nosratola D.
方法.使用流式细胞术，数量和表型的循环DC [髓样DC（mDC）和浆细胞样DC（pDC）]进行了定量的透析前和透析后的血液样本从20个终末期肾病患者维持血液透析。10名正常人作为对照。另外，通过检测DC中共刺激分子CD 86、抗原呈递分子HLA-DR的表达以及TNF α、IFN α和IL-6的产生，来确定DC的活化水平及其对脂多糖（LPS）刺激的反应。与对照组相比，ESRD患者透析前循环树突状细胞计数显著降低，透析后进一步下降。pDC数量的减少比mDC更显著。LPS诱导的CD 86上调的幅度在研究组之间以及透析前和透析后样品之间相当。然而，在透析后样本中，LPS诱导的TNF α产生显著减少，在研究组之间以及透析前和透析后样本中，IL-6和IFN α产生无显著差异。ESRD导致显著的DC耗竭，这主要是由于浆细胞样DC亚群减少。血液透析过程加剧了DC耗竭并损害LPS诱导的TNF α产生。
Methods. Using flow cytometry, the number and phenotype of circulating DC [myeloid DC (mDC) and plasmacytoid DC (pDC)] were quantified in pre- and post-dialysis blood samples from 20 ESRD patients maintained on haemodialysis. Ten normal individuals served as controls. In addition, the level of DC activation and their response to lipopolysaccharide (LPS) stimulation were determined by assessing expression of co-stimulatory molecule, CD86, and antigen-presenting molecule, HLA-DR, as well as production of TNF alpha, IFN alpha and IL-6.Results. Compared to the control group, the circulating dendritic cell count was significantly reduced in the ESRD patients before dialysis and declined further after dialysis. The reduction in pDC numbers was more striking than mDC. The magnitude of the LPS-induced up-regulation of CD86 was comparable among the study groups as well as pre- and post-dialysis samples. However, LPS-induced TNF alpha production was significantly reduced in the post-dialysis samples with no significant difference in IL-6 and IFN alpha productions among the study groups and in pre- and post-dialysis samples.Conclusions. ESRD results in significant DC depletion which is largely due to diminished plasmacytoid DC subset. Haemodialysis procedure intensifies DC depletion and impairs LPS-induced TNF alpha production.