ATP mediates rapid microglial response to local brain injury in vivo
ATP mediates rapid microglial response to local brain injury in vivo
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DOI：
10.1038/nn1472
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发表时间：
2005-06-01
影响因子：
25
通讯作者：
Gan, WB
中科院分区：
文献类型：
--
作者：
Davalos, D;Grutzendler, J;Gan, WB
实质小胶质细胞是大脑的主要免疫细胞。对绿色荧光蛋白标记的小胶质细胞进行的延时双光子成像显示，在完整的小鼠皮质中，小胶质细胞突起的精细末端具有高度动态性。在脑外伤时，小胶质细胞突起在细胞体不移动的情况下迅速且自主地聚集在损伤部位，在健康组织和受损组织之间形成一道潜在的屏障。这种快速的趋化反应可通过局部注射三磷酸腺苷（ATP）来模拟，并且可被ATP水解酶三磷酸腺苷双磷酸酶或G蛋白偶联嘌呤能受体和连接蛋白通道的阻断剂所抑制，这些受体和通道在星形胶质细胞中高度表达。在存在三磷酸腺苷双磷酸酶和连接蛋白通道抑制剂的情况下，小胶质细胞突起的基线运动性也显著降低。因此，细胞外ATP调节完整大脑中小胶质细胞分支的动态，并且它从受损组织和周围星形胶质细胞的释放介导了小胶质细胞对损伤的快速反应。
Parenchymal microglia are the principal immune cells of the brain. Time-lapse two-photon imaging of GFP-labeled microglia demonstrates that the fine termini of microglial processes are highly dynamic in the intact mouse cortex. Upon traumatic brain injury, microglial processes rapidly and autonomously converge on the site of injury without cell body movement, establishing a potential barrier between the healthy and injured tissue. This rapid chemotactic response can be mimicked by local injection of ATP and can be inhibited by the ATP-hydrolyzing enzyme apyrase or by blockers of G protein - coupled purinergic receptors and connexin channels, which are highly expressed in astrocytes. The baseline motility of microglial processes is also reduced significantly in the presence of apyrase and connexin channel inhibitors. Thus, extracellular ATP regulates microglial branch dynamics in the intact brain, and its release from the damaged tissue and surrounding astrocytes mediates a rapid microglial response towards injury.