The influence of IgG density and macrophage Fc (gamma) receptor cross-linking on phagocytosis and IL-10 production.
The influence of IgG density and macrophage Fc (gamma) receptor cross-linking on phagocytosis and IL-10 production.
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DOI：
10.1016/j.imlet.2010.07.004
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发表时间：
2010-10-30
影响因子：
4.4
通讯作者：
Mosser, David M.
中科院分区：
文献类型：
--
作者：
Gallo, Paul;Goncalves, Ricardo;Mosser, David M.
我们以前已经证明，除了免疫复合物（IC）刺激巨噬细胞可以深刻地影响细胞因子的产生。在目前的工作中，我们试图确定免疫复合物上的IgG的密度，所述免疫复合物是介导吞噬作用、抑制IL-12产生和诱导刺激的巨噬细胞产生IL-10所必需的。我们开发了具有可预测的表面结合免疫球蛋白平均密度的免疫复合物。我们表明，一个阈值量的IgG是必要的介导的IC附着到巨噬细胞。在IgG的密度逐渐升高时，Fc受体介导的吞噬作用导致IL-12产生的抑制，然后诱导IL-10。这两种细胞因子的相互变化发生时，少至一个最佳调理SRBC结合每巨噬细胞。免疫复合物诱导的巨噬细胞IL-10与MAP激酶ERK的激活相关，ERK作为IgG密度的函数逐渐增加。我们得出结论，通过巨噬细胞Fc γ受体的信号转导作为信号强度的函数而变化。在中等IgG密度下，特别是在存在补体的情况下，在不存在细胞因子改变的情况下发生有效的吞噬作用。在略高的IgG密度下，IL-12的产生被关闭，最终发生IL-10诱导。因此，由FcγR连接产生的无数事件取决于免疫复合物的密度，从而允许Fc受体根据受体交联的程度微调细胞应答。
We have previously demonstrated that the addition of immune complexes (IC) to stimulated macrophages could profoundly influence cytokine production. In the present work we sought to determine the density of IgG on immune complexes necessary to mediate phagocytosis, inhibit IL-12 production and induce IL-10 production from stimulated macrophages. We developed immune complexes with predictable average densities of surface-bound immunoglobulin. We show that a threshold amount of IgG was necessary to mediate attachment of IC to macrophages. At progressively higher densities of IgG, Fc receptor-mediated phagocytosis resulted in an inhibition of IL-12 production and then an induction of IL-10. The reciprocal alterations in these two cytokines occurred when as little as one optimally-opsonized SRBC was bound per macrophage. Macrophage IL-10 induction by immune complexes was associated with the activation of the MAP Kinase, ERK, which was progressively increased as a function of IgG density. We conclude that signal transduction through the macrophage Fc gamma receptors vary as a function of signal strength. At moderate IgG densities, especially in the presence of complement, efficient phagocytosis occurs in the absence of cytokine alterations. At slightly higher IgG densities IL-12 production is shut off and eventually IL-10 induction occurs. Thus, the myriad events emanating from FcγR ligation depends on the density of immune complexes, allowing the Fc receptors to fine-tune cellular responses depending on the extent of receptor cross-linking.
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影响因子：
--
作者：
Mullazehi, Mohammed;Mathsson, Linda;Ronnelid, Johan
通讯作者：
Ronnelid, Johan
影响因子：
4.4
作者：
Gerber, JS;Mosser, DM
通讯作者：
Mosser, DM
IgG免疫复合物在感染Leishmania的感染过程中的作用。
影响因子：
15.3
作者：
Miles, SA;Conrad, SM;Aves, RG;Jeronimo, SMB;Mosser, DM
通讯作者：
Mosser, DM
DOI：
10.1084/jem.186.7.1027
发表时间：
1997-10-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Crowley MT;Costello PS;Fitzer-Attas CJ;Turner M;Meng F;Lowell C;Tybulewicz VL;DeFranco AL
通讯作者：
DeFranco AL
影响因子：
32.4
作者：
Nimmerjahn, F;Bruhns, P;Ravetch, JV
通讯作者：
Ravetch, JV