Unique activation status of peripheral blood mononuclear cells at acute phase of Kawasaki disease
Unique activation status of peripheral blood mononuclear cells at acute phase of Kawasaki disease
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DOI：
10.1111/j.1365-2249.2009.04073.x
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发表时间：
2010-05-01
影响因子：
4.6
通讯作者：
Hara, T.
中科院分区：
文献类型：
--
作者：
Ikeda, K.;Yamaguchi, K.;Hara, T.
虽然川崎病（KD）的特点是急性期免疫系统明显激活，血清促炎细胞因子和趋化因子升高，但这些化学介质的主要来源仍有争议。采用流式细胞术、DNA芯片和定量逆转录聚合酶链反应分析外周血单个核细胞（PBMCs）的活化状态。急性期KD自然杀伤细胞和γ δ T细胞中CD69+细胞的比例均显著高于恢复期KD。基因芯片分析显示，NAIP、IPAF、S100A9、FCGR1A、GCA等5个基因在急性期KD中上调，且急性期KD所涉及的通路与先天免疫系统密切相关。损伤相关分子模式分子（DAMP） （S100A9和S100A12）基因在急性期KD患者中的相对表达水平显著高于恢复期KD患者，而TNFA、IL1B和IL6基因在KD患者与健康对照组之间的相对表达水平无显著差异。在KD患者中未观察到PBMCs细胞内肿瘤坏死因子- α、白细胞介素-10和干扰素- γ的产生。目前的数据表明，PBMCs表现出一种独特的激活状态，即DAMP基因高表达，促炎细胞因子基因低表达，先天免疫系统可能在KD的发病和病理生理中发挥作用。
P>Although Kawasaki disease (KD) is characterized by a marked activation of the immune system with elevations of serum proinflammatory cytokines and chemokines at acute phase, the major sources for these chemical mediators remain controversial. We analysed the activation status of peripheral blood mononuclear cells (PBMCs) by flow cytometry, DNA microarray and quantitative reverse transcription-polymerase chain reaction. The proportions of CD69+ cells in both natural killer cells and gamma delta T cells at acute-phase KD were significantly higher than those at convalescent-phase KD. Microarray analysis revealed that five genes such as NAIP, IPAF, S100A9, FCGR1A and GCA up-regulated in acute-phase KD and the pathways involved in acute phase KD were related closely to the innate immune system. The relative expression levels of damage-associated molecular pattern molecule (DAMP) (S100A9 and S100A12) genes in PBMCs at acute-phase KD were significantly higher than those at convalescent-phase KD, while those of TNFA, IL1B and IL6 genes were not significantly different between KD patients and healthy controls. Intracellular production of tumour necrosis factor-alpha, interlaukin-10 and interferon-gamma in PBMCs was not observed in KD patients. The present data have indicated that PBMCs showed a unique activation status with high expression of DAMP genes but low expression of proinflammatory cytokine genes, and that the innate immune system appears to play a role in the pathogenesis and pathophysiology of KD.