Reversing lipopolysaccharide toxicity by ligating the macrophage Fcγ receptors
Reversing lipopolysaccharide toxicity by ligating the macrophage Fcγ receptors
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DOI：
10.4049/jimmunol.166.11.6861
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发表时间：
2001-06-01
影响因子：
4.4
通讯作者：
Mosser, DM
中科院分区：
文献类型：
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作者：
Gerber, JS;Mosser, DM
我们的实验室先前已经证明，巨噬细胞上吞噬细胞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 Gammar结扎后细胞因子对多种炎症刺激的反应。巨噬细胞用脂多糖、脂磷壁酸、CD40配体或低分子透明质酸刺激。所有这些刺激在本质上都是促炎的，诱导产生高水平的IL-12，但只产生少量的IL-10。Fc Gammar与这些刺激物结合后可产生抗炎作用，抑制IL-12的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。虽然IL-12的生物合成被几种巨噬细胞受体所共有，但IL-10的诱导是Fc Gammar所特有的。在内毒素血症的小鼠模型中，这些观察结果的生物学相关性被检验，在该模型中，Fc Gammar结扎诱导IL-10的快速产生并阻止IL-12的合成。小鼠可被动免疫内毒素抗体，逆转炎性细胞因子的产生，而Fc-Gamma基因所在巨噬细胞的转移可使小鼠免于致死性内毒素血症。因此，巨噬细胞Fc-Gammar的结扎可以被用来防止不适当的炎症细胞因子反应。
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 Fc gammaR 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 Fc gammaR 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 Fc gammaR. The biological relevance of these observations was examined in murine models of endotoxemia, in which Fc gammaR 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 Fc gammaR had been ligated could rescue mice from lethal endotoxemia. Thus, the ligation of the macrophage Fc gammaR can be exploited to prevent inappropriate inflammatory cytokine responses.