Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord.
Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord.
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DOI：
10.1523/jneurosci.3257-09.2009
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发表时间：
2009-10-28
期刊：
影响因子：
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通讯作者：
Popovich PG
中科院分区：
文献类型：
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作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
巨噬细胞主导中枢神经系统（CNS）损伤的部位，在那里它们促进损伤和修复。这些不同的作用可能是由不同的巨噬细胞亚群引起的，即“经典活化”的促炎细胞（M1）或“替代活化”的抗炎细胞（M2）。在这里，我们发现M1巨噬细胞反应在创伤性脊髓损伤部位被迅速诱导并维持，并且这种反应压倒了相对较小且短暂的M2巨噬细胞反应。高M1:M2巨噬细胞比例对中枢神经系统修复具有重要意义。事实上，我们提供的新数据显示，只有M1巨噬细胞具有神经毒性，M2巨噬细胞促进成人感觉轴突的再生生长反应，即使在抑制底物（如蛋白聚糖和髓磷脂）主导中枢神经系统损伤位点的情况下也是如此。总之，这些数据表明，将常驻小胶质细胞和浸润性血液单核细胞分化为M2或“选择性”活化的巨噬细胞表型可以促进中枢神经系统修复，同时限制继发性炎症介导的损伤。
Macrophages dominate sites of central nervous system (CNS) injury where they promote both injury and repair. These divergent effects may be caused by distinct macrophage subsets, i.e., “classically-activated” pro-inflammatory (M1) or “alternatively-activated” anti-inflammatory (M2) cells. Here, we show that an M1 macrophage response is rapidly induced then maintained at sites of traumatic spinal cord injury and that this response overwhelms a comparatively smaller and transient M2 macrophage response. The high M1:M2 macrophage ratio has significant implications for CNS repair. Indeed, we present novel data showing that only M1 macrophages are neurotoxic and M2 macrophages promote a regenerative growth response in adult sensory axons, even in the context of inhibitory substrates that dominate sites of CNS injury (e.g., proteoglycans and myelin). Together, these data suggest that polarizing the differentiation of resident microglia and infiltrating blood monocytes toward an M2 or “alternatively” activated macrophage phenotype could promote CNS repair while limiting secondary inflammatory-mediated injury.