Immune phenotypes of microglia in human neurodegenerative disease: challenges to detecting microglial polarization in human brains.
Immune phenotypes of microglia in human neurodegenerative disease: challenges to detecting microglial polarization in human brains.
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DOI：
10.1186/s13195-015-0139-9
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发表时间：
2015-08-19
期刊：
影响因子：
--
通讯作者：
Lue LF
中科院分区：
文献类型：
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作者：
Walker DG;Lue LF
脑中的炎症反应，其可以通过小胶质细胞（脑驻留巨噬细胞）的性质变化来证明，是人类神经退行性疾病的共同特征。不同的单核细胞/巨噬细胞表型已经通过细胞因子、受体和其他标志物表达的变化来定义，作为对不同类别刺激的响应。单核细胞、巨噬细胞和小胶质细胞可以具有一系列表型，其具有取决于其微环境的相关性质。巨噬细胞/小胶质细胞极化状态已被定义为经典激活（M1）、交替激活（M2 a）、II型交替激活（M2 b）或获得性失活（M2 c）。用于鉴定人脑中小胶质细胞表型的可用标记物仍然有限;那些可用的标记物提供了关于在来自诸如阿尔茨海默病、帕金森病和多发性硬化症的疾病的组织中观察到的小胶质细胞的功能或极化状态的不完整信息。最广泛使用的标记来描述人类大脑，特别是患病大脑中的活化小胶质细胞，是HLA-DR，主要组织相容性复合体II蛋白。HLA-DR阳性小胶质细胞可以具有广泛的活化形态，其不仅受疾病病理学影响，而且受其分化状态和脑区域影响。另外两种广泛用于识别人脑中小胶质细胞的标记物是离子钙结合衔接分子-1和CD 68。虽然它们在患病大脑中的表达会发生变化，但这些标记物对不同的表型没有特异性。多年来，已经有研究试图进一步定义小胶质细胞的特性，特别是在阿尔茨海默病的大脑中。大多数研究采用免疫组织化学技术来识别组织切片中的小胶质细胞，但该领域的最新进展允许从大脑中立即分离小胶质细胞后进行基因表达谱分析。我们将回顾哪些标记可能更好地定义不同的激活表型的小胶质细胞在人脑中，以及它们是否适合目前的小胶质细胞极化计划。
Inflammatory responses in the brain, which can be demonstrated by changes in properties of microglia, the brain-resident macrophages, are a common feature of human neurodegenerative diseases. Different monocyte/macrophage phenotypes have been defined by changes in expression of cytokines, receptors and other markers as a response to different classes of stimuli. Monocytes, macrophages and microglia can have a range of phenotypes with associated properties depending on their microenvironment. Macrophage/microglia polarization states have been defined as classical activation (M1), alternative activation (M2a), type II alternative activation (M2b) or acquired deactivation (M2c). Available markers for identifying microglial phenotypes in human brains are still limited; those available provide incomplete information on the functions or polarization states of microglia observed in tissues from diseases such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. The most widely used marker to describe activated microglia in human brains, particularly diseased brains, has been HLA-DR, the major histocompatibility complex II protein. HLA-DR-positive microglia can have a wide range of activation morphologies that are affected not only by disease pathology, but also by their differentiation states and brain regions. Two other widely used markers to identify microglia in human brains are ionized calcium binding adaptor molecule-1 and CD68. Although their expression changes in diseased brains, these markers do not show specificity for different phenotypes. Over the years there have been studies with additional markers that attempt to further define microglial properties, particularly in Alzheimer’s disease brains. Most studies have employed immunohistochemical techniques to identify microglia in tissue sections, but recent advances in this field have allowed gene expression profiling of microglia upon immediate isolation from brains. We will review which markers might better define different activation phenotypes of microglia in human brains and whether they fit into current microglial polarization schemes.