Faculty of Life Science, University of Manchester, Michael Smith Building D3315, Manchester, M13 9PT, UK.
Cell Mol Life Sci. 2011 Sep;68(18):3095-107. doi: 10.1007/s00018-010-0609-y. Epub 2010 Dec 28.
Plasticity is a well-known property of macrophages that is controlled by different changes in environmental signals. Macrophage polarization is regarded as a spectrum of activation phenotypes adjusted from one activation extreme, the classic (M1), to the other, the alternative (M2) activation. Here we show, in vitro and in vivo, that both M1 and M2 macrophage phenotypes are tightly coupled to specific patterns of gene expression. Novel M2-associated markers were characterized and identified as genes controlling the extracellular metabolism of ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with PPi dampens both NLR and TLR signaling and thus mediates cytokine production. In this context extracellular PPi enhanced the resolution phase of a murine peritonitis model via a decrease in pro-inflammatory cytokine production. Therefore, our study reveals an additional level of plasticity modulating the resolution of inflammation.
可塑性是巨噬细胞的一个众所周知的特性，由不同的环境信号变化控制。巨噬细胞极化被认为是一种从一种激活极端（经典的 M1）到另一种激活极端（替代的 M2）的激活表型调节的谱。在这里，我们在体外和体内都表明，M1 和 M2 巨噬细胞表型都与特定的基因表达模式紧密相关。我们对新型 M2 相关标记物进行了特征描述，并将其鉴定为控制细胞外 ATP 代谢生成焦磷酸盐（PPi）的基因。用 PPi 刺激 M1 巨噬细胞可抑制 NLR 和 TLR 信号，从而介导细胞因子的产生。在这种情况下，细胞外 PPi 通过减少促炎细胞因子的产生，增强了小鼠腹膜炎模型的消退阶段。因此，我们的研究揭示了一个额外的调节炎症消退的可塑性水平。
