Proteomic Signature Reveals Modulation of Human Macrophage Polarization and Functions Under Differing Environmental Oxygen Conditions
Proteomic Signature Reveals Modulation of Human Macrophage Polarization and Functions Under Differing Environmental Oxygen Conditions
复制标题
蛋白质组学特征揭示不同环境氧条件下人巨噬细胞极化和功能的调节
DOI：
10.1074/mcp.ra117.000082
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发表时间：
2017-12-01
影响因子：
7
通讯作者：
Millet, Arnaud
中科院分区：
文献类型：
--
作者：
Court, Magali;Petre, Graciane;Millet, Arnaud
巨噬细胞是先天免疫细胞，由于具有高度的可塑性，可以对大量环境刺激做出反应。这些细胞参与体内平衡的多种组织功能，并且在病理环境中发挥重要作用。巨噬细胞的激活状态决定其功能方向，受到细胞环境的强烈影响。大量巨噬细胞文献致力于从分子角度更好地定义极化。现在人们普遍认为，需要多维极化模型来掌握环境信号控制的广泛表型库。这里提出的研究的目的之一是在蛋白质水平上提供人类巨噬细胞各种极化的分子特征，以更好地定义不同的巨噬细胞激活状态。为了研究人单核细胞来源的巨噬细胞中的蛋白质组与其极化状态的函数关系，我们对凝胶内分级和 LysC/胰蛋白酶消化的蛋白质使用了无标记定量方法。总共对所有偏振态的 5102 种蛋白质进行了鉴定和定量。鉴定并验证了新的偏振特异性标记。由于氧张力是组织中的一个重要环境参数，因此我们探讨了大气成分 (18.6% O-2) 或“组织含氧量正常”(3% O-2) 下的环境氧张力如何影响我们对巨噬细胞极化的分类。比较结果揭示了新的极化特异性标记物，这表明在表征巨噬细胞激活状态时应考虑环境氧水平。蛋白质组筛选揭示了人类巨噬细胞中的各种偏振特异性蛋白质和氧传感器。一个例子是花生四烯酸 15-脂氧合酶 (ALOX15)，一种 IL4/IL13 极化特异性蛋白，它在低氧条件下上调，并与凋亡细胞吞噬率的增加有关。这些结果说明在研究巨噬细胞极化时需要考虑氧水平等物理化学参数，以便正确评估其在组织中的功能。
Macrophages are innate immune cells which can react to a large number of environmental stimuli thanks to a high degree of plasticity. These cells are involved in a variety of tissue functions in homeostasis, and they play essential roles in pathological contexts. Macrophages' activation state, which determines their functional orientation, is strongly influenced by the cellular environment. A large body of macrophage literature is devoted to better defining polarizations from a molecular viewpoint. It is now accepted that a multidimensional model of polarization is needed to grasp the broad phenotype repertoire controlled by environmental signals. The study presented here aimed, among other goals, to provide a molecular signature of various polarizations in human macrophages at the protein level to better define the different macrophage activation states. To study the proteome in human monocyte-derived macrophages as a function of their polarization state, we used a label-free quantification approach on in-gel fractionated and LysC/Trypsin digested proteins. In total, 5102 proteins were identified and quantified for all polarization states. New polarization-specific markers were identified and validated. Because oxygen tension is an important environmental parameter in tissues, we explored how environmental oxygen tension, at either atmospheric composition (18.6% O-2) or "tissue normoxia" (3% O-2), affected our classification of macrophage polarization. The comparative results revealed new polarization-specific makers which suggest that environmental oxygen levels should be taken into account when characterizing macrophage activation states. The proteomic screen revealed various polarization-specific proteins and oxygen sensors in human macrophages. One example is arachidonate 15-lipoxygenase (ALOX15), an IL4/IL13 polarization-specific protein, which was upregulated under low oxygen conditions and is associated with an increase in the rate of phagocytosis of apoptotic cells. These results illustrate the need to consider physicochemical parameters like oxygen level when studying macrophage polarization, so as to correctly assess their functions in tissue.