Lipopolysaccharide induces rapid production of IL-10 by monocytes in the presence of apoptotic neutrophils
Lipopolysaccharide induces rapid production of IL-10 by monocytes in the presence of apoptotic neutrophils
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DOI：
10.4049/jimmunol.168.4.1968
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发表时间：
2002-02-15
影响因子：
4.4
通讯作者：
Reen, DJ
中科院分区：
文献类型：
--
作者：
Byrne, A;Reen, DJ
越来越多的证据表明，凋亡中性粒细胞在巨噬细胞和树突状细胞吞噬后的炎症调节和解决中发挥着积极作用。然而，它们对新招募到炎症部位的活化血液单核细胞的影响尚未确定。在这项工作中，我们研究了凋亡中性粒细胞对 LPS 激活的单核细胞产生细胞因子的影响。在凋亡中性粒细胞存在的情况下，用 LPS 刺激单核细胞 18 小时，会引发免疫抑制细胞因子反应，IL-10 和 TGF-β 的产生增强，而 TNF-α 和 IL-1β 细胞因子的产生极少。时间动力学研究表明，在凋亡中性粒细胞存在的情况下，IL-10 的产生显着加速，而 TNF-α 和 IL-1β 的产生持续减少。这种促炎产生的抑制不能通过消耗 IL-10 或 TGF-β 或添加外源 IFN-γ 来逆转。使用 Transwell 实验证明，单核细胞与凋亡细胞接触是诱导免疫抑制单核细胞反应所必需的。单核细胞的反应与人单核细胞来源的巨噬细胞的反应形成鲜明对比，其中 IL-10 的产生减少。我们从这些数据中得出结论，活化的单核细胞和凋亡的中性粒细胞之间的相互作用产生了独特的反应，该反应将活化的单核细胞从炎症级联的启动子转变为准备使其自身和其他细胞失活的细胞。
There is growing evidence that apoptotic neutrophils have an active role to play in the regulation and resolution of inflammation following phagocytosis by macrophages and dendritic cells. However, their influence on activated blood monocytes, freshly recruited to sites of inflammation, has not been defined. In this work, we examined the effect of apoptotic neutrophils on cytokine production by LPS-activated monocytes. Monocytes stimulated with LPS in the presence of apoptotic neutrophils for 18 h elicited an immunosuppressive cytokine response, with enhanced IL-10 and TGF-beta production and only minimal TNF-alpha and IL-1beta cytokine production. Time-kinetic studies demonstrated that IL-10 production was markedly accelerated in the presence of apoptotic neutrophils, whereas there was a sustained reduction in the production of TNF-alpha and IL-1beta. This suppression of proinflammatory production was not reversible by depletion of IL-10 or TGF-beta or by addition of exogenous IFN-gamma. It was demonstrated, using Transwell experiments, that monocyte-apoptotic cell contact was required for induction of the immunosuppressive monocyte response. The response of monocytes contrasted with that of human monocyte-derived macrophages in which there was a reduction in IL-10 production. We conclude from these data that interaction between activated monocytes and apoptotic neutrophils creates a unique response, which changes an activated monocyte from being a promoter of the inflammatory cascade into a cell primed to deactivate itself and other cells.