Kigerl Kristina A, Gensel John C, Ankeny Daniel P, Alexander Jessica K, Donnelly Dustin J, Popovich Phillip G
Center for Brain and Spinal Cord Repair, Ohio State University, Columbus, Ohio 43210, USA.
J Neurosci. 2009 Oct 28;29(43):13435-44. doi: 10.1523/JNEUROSCI.3257-09.2009.
Macrophages dominate sites of CNS injury in which they promote both injury and repair. These divergent effects may be caused by distinct macrophage subsets, i.e., "classically activated" proinflammatory (M1) or "alternatively activated" anti-inflammatory (M2) cells. Here, we show that an M1 macrophage response is rapidly induced and 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.
巨噬细胞在中枢神经系统损伤部位占主导地位，在这些部位它们既促进损伤又促进修复。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”的促炎性（M1）或“替代活化”的抗炎性（M2）细胞。在这里，我们表明，M1巨噬细胞反应在创伤性脊髓损伤部位迅速诱导并随后维持，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巨噬细胞比率对中枢神经系统修复具有重要意义。事实上，我们提供的新数据表明，只有M1巨噬细胞具有神经毒性，而M2巨噬细胞即使在中枢神经系统损伤部位占主导的抑制性底物（如蛋白聚糖和髓磷脂）存在的情况下，也能促进成年感觉轴突的再生生长反应。总之，这些数据表明，将驻留小胶质细胞和浸润血单核细胞的分化极化为M2或“替代”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。
