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The role of peripheral blood monocytes/macrophages in systemic response syndrome

外周血单核细胞/巨噬细胞在全身反应综合征中的作用

基本信息

批准号：
11470171
负责人：
FURUKAWA Susumu
金额：
$ 8.58万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470171/
关键词：
SIRS sepsis Kawasaki disease monocytes macrophages M1 M2 Th1 Th2 nuclear factor kappa (NF-_KB)nuclear factor kappa B(NF-κB)IL-10 IL-12 CD14^+CD16^+モノサイト成熟マクロファージ PM2K

项目摘要

Recently, sepsis and Kawasaki disease (KD) are identified as systemic response syndrome (SIRS). We investigated the role of peripheral blood monocytes/macrophages in the state of SIRS.1) We investigated peripheral blood CD14 + CD16 + monocytes subpopulation by flow cytometry, and serum levels of interleukin (IL) -10 and IL -12 using a sandwich enzyme-linked immunosorbent assay. We found that CD14 + CD16 + monocytes were more increased and the serum levels of IL -10, but not IL -12, were higher during acute SIRS than convalescent stage and controls. 2) We also examined peripheral blood monocytes using a monoclonal antibody, PM-2K, which recognizes mature macrophages but not monocytes. Approximately 15-20% of peripheral blood CD14 + monocytes/macrophages from KD patients were positive for PM-2K antibody. Monocytes partly differentiate into macrophages in the peripheral circulation during the acute SIRS. 3) T helper (Th) 1 and Th2 subsets have been implicated in the regulation of many immune responses. We investigated peripheral blood T cells of SIRS, focusing on Th1 and Th2 imbalance, using intracellular cytokine staining and analysis of the cytokine-producing T cells by flow cytometry. We observed a decrease of IFN-γ-producing CD3 + T cells during the acute stage of SIRS. 4) We investigated the activation of transcription factor NF-_KB for genes that encode the proinflammatory cytokines in CD14 + monocytes/macrophages and CD3 + T cells in peripheral blood by means of Western blot and flow cytometric analyses. We found that NF-_KB activation was more increased in CD14 + monocytes/macrophages than in CD3 + T cells in all children during the acute stage.In conclusion, activation of monocytes/macrophages plays a central role in the pathogenesis of SIRS.

最近，败血症和川崎病（KD）被确定为全身反应综合征（SIRS）。我们研究了外周血单核细胞/巨噬细胞在 SIRS 状态中的作用。1）我们通过流式细胞术研究了外周血 CD14 + CD16 + 单核细胞亚群，并使用夹心酶联免疫吸附测定法研究了白细胞介素（IL）-10 和 IL -12 的血清水平。我们发现，急性 SIRS 期间 CD14 + CD16 + 单核细胞更多地增加，并且 IL -10 的血清水平高于恢复期和对照，但 IL -12 的血清水平则更高。 2) 我们还使用单克隆抗体 PM-2K 检测了外周血单核细胞，该抗体可识别成熟的巨噬细胞，但不能识别单核细胞。 KD 患者的外周血 CD14 + 单核细胞/巨噬细胞中约 15-20% 的 PM-2K 抗体呈阳性。急性 SIRS 期间，外周循环中的单核细胞部分分化为巨噬细胞。 3) 辅助性 T (Th) 1 和 Th2 亚群与许多免疫反应的调节有关。我们研究了 SIRS 的外周血 T 细胞，重点关注 Th1 和 Th2 失衡，使用细胞内细胞因子染色并通过流式细胞术分析产生细胞因子的 T 细胞。我们观察到 SIRS 急性期产生 IFN-γ 的 CD3 + T 细胞减少。 4）我们通过蛋白质印迹和流式细胞术分析，研究了外周血中CD14+单核细胞/巨噬细胞和CD3+T细胞中编码促炎细胞因子的基因转录因子NF-_KB的激活。我们发现，在所有儿童的急性期，CD14 + 单核细胞/巨噬细胞中的 NF-_KB 激活比 CD3 + T 细胞中的 NF-_KB 激活更多。总之，单核细胞/巨噬细胞的激活在 SIRS 的发病机制中起着核心作用。