Assessing Activation States in Microglia
Assessing Activation States in Microglia
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DOI：
10.2174/187152710791012053
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发表时间：
2010-04-01
影响因子：
3
通讯作者：
Wilcock, Donna M.
中科院分区：
文献类型：
--
作者：
Colton, Carol A.;Wilcock, Donna M.
自从小胶质细胞最初被鉴定为大脑先天免疫反应的主要参与者以来，小胶质细胞的激活已经被广泛研究。最近的研究表明，小胶质细胞的反应是异质性的，需要更精确的定义，他们参与疾病的功能结果。与其他组织巨噬细胞类似，小胶质细胞以预先编程的方式对CNS中的炎性或损伤性刺激做出反应，其设计为杀死并为疾病的修复和解决奠定基础。对急性免疫应答的体外研究提供了关于活化巨噬细胞的启动、信号传导途径和产物的关键信息。然而，在慢性神经退行性疾病，如阿尔茨海默氏病，在体内分析是至关重要的了解长期的疾病过程中，我们的知识的综合组织免疫反应和这种免疫活性的结果，神经元和其他神经胶质细胞在疾病的扩展过程是比较有限的。这部分是由于小胶质细胞激活状态的复杂性以及小胶质细胞在密集神经元网络中的位置。在慢性神经炎性疾病期间，经典激活、替代激活和获得性失活均在脑中发现，并且可能表现出表达水平的区域差异。这篇综述将确定可用于探索大脑炎症状态的“标记物”，并将讨论当这些细胞活性因子表达时可能的功能结果。提供了一个基础广泛的功能视图，旨在更充分地探索控制慢性疾病进展的炎症毒性和炎症消退因子之间的平衡。
Since the original identification of microglia as a principal player in the brain's innate immune response, microglial activation has been widely studied. Recent studies suggest that microglial responses are heterogeneous, requiring a more precise definition of the functional outcomes of their participation in disease. Similarly to other tissue macrophages, microglia respond to inflammatory or injurious stimuli in the CNS in a pre-programmed manner that is designed to both kill and to set the stage for repair and resolution of the disease. In vitro studies on acute immune responses have provided key information on the initiation, signaling pathways and products of activated macrophages. However, in chronic neurodegenerative diseases such as Alzheimer's disease where in vivo analyses are critical to understanding the long-term disease processes, our knowledge of the integrated tissue immune response and the outcome of this immune activity to neurons and other glia over the extended course of disease is more limited. This is due in part to the complexity of microglial activation states and to the location of microglia in a dense neuronal network. Classical activation, alternative activation and acquired deactivation are each found in the brain during chronic neuroinflammatory diseases and may demonstrate regional differences in expression levels. This review will identify "markers" that can be used to explore inflammatory states in the brain and will discuss the likely functional outcomes when these cytoactive factors are expressed. A broad-based functional view is provided that is designed to more fully explore the balance between inflammo-toxic and inflammo-resolution factors that govern chronic disease progression.