University of California, Irvine, USA.
Am J Nephrol. 2010;31(3):247-54. doi: 10.1159/000276764. Epub 2010 Jan 15.
End-stage renal disease (ESRD) is simultaneously associated with inflammation, impaired immunity and increased susceptibility to microbial infections. Innate immune cells, monocytes and polymorphonuclear leukocytes (PMN) recognize pathogens via toll-like receptors (TLR) triggering phagocytosis, cellular activation and secretion of inflammatory cytokines. Data on expression and function of TLRs in ESRD are limited.
Blood samples from 21 stable ESRD patients and 21 normal controls were processed for TLR2, TLR4, TLR7 and TLR 9 expression on monocytes and PMN by flow cytometry. TLR activity was examined by determining the response to TLR4 and TLR2 ligands.
The ESRD group exhibited significant upregulation of TLR2 and TLR4 (but not TLR7 or TLR 9) expressions on monocytes and of TLR4 on PMN. This was coupled with heightened cytokine production in response to TLR4 activation with lipopolysaccharide. However, the response to TLR2 stimulation with peptidoglycan was unchanged in the ESRD group.
Monocyte TLR2 and TLR4 and neutrophil TLR4 expressions and TLR4 activity are increased hemodialysis patients, representing another dimension of ESRD-associated inflammation.
终末期肾病(ESRD)同时与炎症、免疫受损和增加对微生物感染的易感性相关。先天免疫细胞,如单核细胞和多形核白细胞(PMN),通过 Toll 样受体(TLR)识别病原体,触发吞噬作用、细胞激活和炎症细胞因子的分泌。关于 ESRD 中 TLR 表达和功能的数据有限。
通过流式细胞术,对 21 例稳定的 ESRD 患者和 21 例正常对照者的血液样本进行 TLR2、TLR4、TLR7 和 TLR9 在单核细胞和 PMN 上的表达检测。通过测定 TLR4 和 TLR2 配体的反应来检测 TLR 活性。
ESRD 组的单核细胞上 TLR2 和 TLR4(但不是 TLR7 或 TLR9)的表达以及 PMN 上 TLR4 的表达显著上调。这与对脂多糖激活 TLR4 时细胞因子产生增加有关。然而,ESRD 组对肽聚糖刺激 TLR2 的反应没有变化。
血液透析患者的单核细胞 TLR2 和 TLR4 以及中性粒细胞 TLR4 的表达和 TLR4 活性增加,这代表了 ESRD 相关炎症的另一个方面。