Differentiated Expression Patterns and Phagocytic Activities of Type 1 and 2 Microglia
Differentiated Expression Patterns and Phagocytic Activities of Type 1 and 2 Microglia
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DOI：
10.1167/iovs.15-18509
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发表时间：
2016-05-01
影响因子：
4.4
通讯作者：
Tanihara, Hidenobu
中科院分区：
文献类型：
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作者：
Haga, Akira;Takahashi, Eri;Tanihara, Hidenobu
目的。本研究的目的是阐明两种亚型小胶质细胞的分化表达模式和吞噬活性。方法：采用大鼠视神经挤压模型，鉴定两种亚型小胶质细胞的表达模式。从混合培养的大鼠神经胶质细胞中分离出原代小胶质细胞。随后，进行轴突碎片吞噬功能的体外实验，分析对免疫调节剂(脂多糖、白介素4和干扰素γ)的反应性，并评价内毒素和白介素4在视神经挤压模型中的作用。免疫印迹实验分析IL-4相关信号分子的表达水平。结果：在视神经挤压模型中，发现小胶质细胞数量增加，并鉴定出一小部分短暂的1型小胶质细胞。2型小胶质细胞比1型小胶质细胞吞噬更多轴突碎片。经内毒素和干扰素-γ处理后，两种亚型小胶质细胞的活性均增强。然而，显示STAT6信号转导激活的1型小胶质细胞的吞噬活性被抗炎细胞因子IL-4刺激显著抑制。结论：本研究揭示了视神经挤压模型中两种小胶质细胞亚群的时间依赖性分布，以及IL-4对1型小胶质细胞吞噬轴突碎片的依赖抑制作用。
PURPOSE. The purpose of this study was to elucidate the differentiated expression patterns and phagocytic activities of two subtypes of microglia.METHODS. A rat optic nerve crush model was used to identify the expression patterns of two subtypes of microglia. Primary microglia were isolated from rat mixed glial cultures. Subsequently, in vitro experiments evaluating the phagocytosis of axonal debris were performed to analyze responsiveness to immunologic modulators (lipopolysaccharide [LPS], interleukin [IL]-4 and interferon [IFN]-gamma), and we assessed the effects of LPS and IL-4 in the optic nerve crush model. The expression levels of IL-4-associated signaling molecules were analyzed in immunoblotting experiments.RESULTS. In the optic nerve crush model, increased numbers of microglia were found, and a minor and transient population was identified as type 1 microglia. The type 2 microglia phagocytosed more axonal debris than the type 1 microglia. The activities of both subtypes of microglia were enhanced by treatment with LPS and IFN-gamma. However, the phagocytic activity of the type 1 microglia, which showed activated STAT6 signal transduction, was significantly inhibited by stimulation with the anti-inflammatory cytokine IL-4. LPS reduced the fragmentation of axons in crushed nerve fibers, whereas the axonal debris remained in IL-4-treated rats subjected to optic nerve crush.CONCLUSIONS. The present study revealed the time-dependent distribution of the two subpopulations of microglia in an optic nerve crush model and IL-4-dependent inhibition of the phagocytosis of axonal debris by type 1 but not type 2 microglia.