Department of Medicine, University of California, Irvine, Irvine, CA, USA.
Nephrol Dial Transplant. 2010 Mar;25(3):737-46. doi: 10.1093/ndt/gfp580. Epub 2009 Nov 9.
Although bacterial infections have dramatically declined as a cause of death in the general population, they remain a major cause of mortality in patients with end-stage renal disease (ESRD). Moreover, the response to vaccination is profoundly impaired in this population. Dendritic cells (DC) are the major antigen-presenting cells that bridge the innate and adaptive immune responses. Activation of DC by pathogens results in secretion of inflammatory cytokines and up-regulation of co-stimulatory molecules. The activated DC prime naïve T and B cells to the captured antigens.
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 TNFalpha, IFNalpha and IL-6.
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 TNFalpha production was significantly reduced in the post-dialysis samples with no significant difference in IL-6 and IFNalpha productions among the study groups and in pre- and post-dialysis samples.
ESRD results in significant DC depletion which is largely due to diminished plasmacytoid DC subset. Haemodialysis procedure intensifies DC depletion and impairs LPS-induced TNFalpha production.
尽管细菌感染作为普通人群的死亡原因已大幅下降，但它们仍是终末期肾病（ESRD）患者死亡的主要原因。此外，该人群对疫苗接种的反应受到严重损害。树突状细胞（DC）是连接先天和适应性免疫反应的主要抗原呈递细胞。病原体激活 DC 会导致炎症细胞因子的分泌和共刺激分子的上调。激活的 DC 使幼稚 T 和 B 细胞对捕获的抗原产生反应。
使用流式细胞术，在接受血液透析的 20 名 ESRD 患者的透析前和透析后血液样本中定量检测循环 DC[髓样 DC（mDC）和浆细胞样 DC（pDC）]的数量和表型。 10 名正常个体作为对照。此外，通过评估共刺激分子 CD86 和抗原呈递分子 HLA-DR 的表达以及 TNFalpha、IFNalpha 和 IL-6 的产生来确定 DC 激活水平及其对脂多糖（LPS）刺激的反应。
与对照组相比，透析前 ESRD 患者的循环树突状细胞计数明显降低，透析后进一步降低。pDC 数量的减少比 mDC 更为明显。研究组之间以及预透析和后透析样本之间，LPS 诱导的 CD86 上调幅度相似。然而，后透析样本中 LPS 诱导的 TNFalpha 产生明显减少，而研究组和预透析和后透析样本中 IL-6 和 IFNalpha 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 亚群减少所致。血液透析程序会加剧 DC 耗竭并损害 LPS 诱导的 TNFalpha 产生。
