Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4
Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4
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DOI：
10.1096/fj.12-204800
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发表时间：
2013-03-01
期刊：
影响因子：
4.8
通讯作者：
Maurer, Marcus
中科院分区：
文献类型：
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作者：
Hendrix, Sven;Kramer, Peter;Maurer, Marcus
肥大细胞 (MC) 在大脑和脑膜中大量存在，在中风和多发性硬化症等神经炎症性疾病中发挥着复杂的作用。在这里，我们发现 MC 缺陷的 Kit(W)/Kit(W-v) 小鼠在脑外伤后病变区域表现出神经退行性增加。此外，MC缺陷小鼠表现出明显更多的脑部炎症，即巨噬细胞/小胶质细胞的存在增加，以及损伤后第4天和第14天T细胞浸润显着增加，以及损伤后第14天星形胶质细胞增多。在这些 MC 缺陷小鼠中，病变区域周围增殖的 Ki67(+) 巨噬细胞/小胶质细胞和星形胶质细胞的数量增加了一倍多。与此同时，MC 缺陷 Kit(W-sh/W-sh) 小鼠在脑外伤后第 4 天表现出巨噬细胞/小胶质细胞的增加，并在第 4 天和第 14 天表现出持续的星形胶质细胞增生。对缺乏一种最相关的 MC 蛋白酶（即小鼠肥大细胞蛋白酶 4 (mMCP-4)）的小鼠的进一步分析表明，在 mMCP-4 敲除小鼠中，星形胶质细胞增生和 T 细胞浸润显着增加。最后，使用 mMCP-4 抑制剂治疗可显着增加巨噬细胞/小胶质细胞数量和星形胶质细胞增生。这些数据表明，MC 在创伤后发挥保护功能，至少部分通过 mMCP-4，通过其蛋白酶抑制加剧的炎症。-Hendrix, S.、Kramer, P.、Pehl, D.、Warnke, K.、Boato, F.、Nelissen, S.、Lemmens, E.、Pejler, G.、Metz, M.、Siebenhaar, F.、Maurer, M.肥大细胞通过肥大细胞特异性食糜酶小鼠肥大细胞蛋白酶 4 来保护免受创伤后脑部炎症。 FASEB J. 27, 920-929 (2013)。 www.fasebj.org
Mast cells (MCs) are found abundantly in the brain and the meninges and play a complex role in neuroinflammatory diseases, such as stroke and multiple sclerosis. Here, we show that MC-deficient Kit(W)/Kit(W-v) mice display increased neurodegeneration in the lesion area after brain trauma. Furthermore, MC-deficient mice display significantly more brain inflammation, namely an increased presence of macrophages/microglia, as well as dramatically increased T-cell infiltration at days 4 and 14 after injury, combined with increased astrogliosis at day 14 following injury. The number of proliferating Ki67(+) macrophages/microglia and astrocytes around the lesion area is more than doubled in these MC-deficient mice. In parallel, MC-deficient Kit(W-sh/W-sh) mice display increased presence of macrophages/microglia at day 4, and persistent astrogliosis at day 4 and 14 after brain trauma. Further analysis of mice deficient in one of the most relevant MC proteases, i.e., mouse mast cell protease 4 (mMCP-4), revealed that astrogliosis and T-cell infiltration are significantly increased in mMCP-4-knockout mice. Finally, treatment with an inhibitor of mMCP-4 significantly increased macrophage/microglia numbers and astrogliosis. These data suggest that MCs exert protective functions after trauma, at least in part via mMCP-4, by suppressing exacerbated inflammation via their proteases.-Hendrix, S., Kramer, P., Pehl, D., Warnke, K., Boato, F., Nelissen, S., Lemmens, E., Pejler, G., Metz, M., Siebenhaar, F., Maurer, M. Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4. FASEB J. 27, 920-929 (2013). www.fasebj.org