Reversing lipopolysaccharide toxicity by ligating the macrophage Fc gamma receptors.
Reversing lipopolysaccharide toxicity by ligating the macrophage Fc gamma receptors.
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DOI：
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发表时间：
2001
影响因子：
4.4
通讯作者：
J. Gerber;D. Mosser
中科院分区：
文献类型：
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作者：
J. Gerber;D. Mosser
我们的实验室先前已经证明，巨噬细胞上的吞噬受体的连接可以影响细胞因子的产生。在这项研究中，我们研究了Fc γ R连接后对多种炎症刺激的细胞因子反应。在体外用LPS、脂磷壁酸、CD 40配体或低分子量透明质酸刺激巨噬细胞。所有这些刺激物在性质上都是促炎性的，诱导产生高水平的IL-12，但仅产生适量的IL-10。Fc γ R与这些刺激物的共连接沿着导致抗炎特性，消除IL-12产生并诱导高水平的IL-10。这两种细胞因子的调节通过两种独立的机制发生。尽管IL-12生物合成的消除是几种巨噬细胞受体共有的特性，但IL-10的诱导对Fc γ R是特异性的。在内毒素血症的鼠模型中检查这些观察结果的生物学相关性，其中Fc γ R连接诱导IL-10的快速产生并阻止IL-12合成。小鼠可以被动免疫LPS的抗体逆转炎症细胞因子的产生，并转移其Fc γ R已连接的巨噬细胞可以拯救小鼠免于致死性内毒素血症。因此，巨噬细胞Fc γ R的连接可用于防止不适当的炎性细胞因子应答。
Our laboratory has previously demonstrated that the ligation of phagocytic receptors on macrophages can influence cytokine production. In this study, we examine the cytokine responses to multiple inflammatory stimuli following FcgammaR ligation. Macrophages were stimulated in vitro with LPS, lipoteichoic acid, CD40 ligand, or low molecular mass hyaluronic acid. All of these stimuli were proinflammatory in character, inducing the production of high levels of IL-12, but only modest amounts of IL-10. The coligation of FcgammaR along with these stimuli resulted in an anti-inflammatory profile, abrogating IL-12 production and inducing high levels of IL-10. The modulation of these two cytokines occurred by two independent mechanisms. Whereas the abrogation of IL-12 biosynthesis was a property shared by several macrophage receptors, the induction of IL-10 was specific to the FcgammaR. The biological relevance of these observations was examined in murine models of endotoxemia, in which FcgammaR ligation induced the rapid production of IL-10 and prevented IL-12 synthesis. Mice could be passively immunized with Abs to LPS to reverse inflammatory cytokine production, and the transfer of macrophages whose FcgammaR had been ligated could rescue mice from lethal endotoxemia. Thus, the ligation of the macrophage FcgammaR can be exploited to prevent inappropriate inflammatory cytokine responses.