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

近年来，败血症和川崎（KD）被认为是全身反应综合征（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CD 14 + CD 16+单核细胞亚群，并使用夹心酶联免疫吸附试验研究了血清白细胞介素（IL）-10和IL-12水平。结果表明，急性期SIRS患者外周血中CD_（14）~+ CD_（16）~+单核细胞明显增多，血清IL-10水平明显升高，而IL-12水平无明显变化。2)我们还使用单克隆抗体PM-2K检查了外周血单核细胞，PM-2K识别成熟的巨噬细胞，但不识别单核细胞。约15-20%的KD患者外周血CD 14+单核细胞/巨噬细胞PM-2K抗体阳性。在急性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细胞（Th）1和Th 2亚群参与了多种免疫应答的调节。我们研究了SIRS患者外周血T细胞，重点是Th 1和Th 2失衡，使用细胞内细胞因子染色和流式细胞术分析产生嘌呤的T细胞。我们观察到在SIRS急性期产生IFN-γ的CD 3 + T细胞减少。4)我们通过Western blot和流式细胞术分析研究了转录因子NF-κ B对编码外周血中CD 14+单核/巨噬细胞和CD 3 + T细胞中促炎细胞因子的基因的激活。结果表明，急性期患儿外周血中CD 14+单核/巨噬细胞NF-κ B的活化水平明显高于CD 3 + T细胞，提示单核/巨噬细胞的活化在SIRS的发病机制中起重要作用。

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.