Requirement of myeloid cells for axon regeneration
Requirement of myeloid cells for axon regeneration
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DOI：
10.1523/jneurosci.1447-08.2008
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发表时间：
2008-09-17
影响因子：
5.3
通讯作者：
Lacroix, Steve
中科院分区：
文献类型：
--
作者：
Barrette, Benoit;Hebert, Marc-Andre;Lacroix, Steve
使用轴突损伤模型和表达由髓样特异性CD 11b启动子调控的突变HSV-1胸苷激酶（TK）基因的CD 11b-TKmt-30小鼠评估CD 11b（+）髓样细胞在轴突再生中的作用。在坐骨神经损伤部位连续给予更昔洛韦可显著降低CD 11b-TKmt-30小鼠远端残端的粒细胞/炎性单核细胞和巨噬细胞数量。更昔洛韦处理的CD 11b-TKmt-30小鼠的轴突再生和运动功能恢复严重受损。这是由不合适的生长环境引起的，而不是神经元再生能力的改变。在缺乏CD 11b（+）细胞的情况下，抑制性髓鞘碎片的清除被阻止，神经营养素的合成被取消，坐骨神经远端残端的血管形成/维持严重受损。在缺乏CD 11b（+）细胞的情况下，脊髓损伤的轴突也不能通过周围神经移植物再生。因此，骨髓细胞通过为受伤的轴突创造允许生长的环境来支持轴突再生和功能恢复。
The role of CD11b(+) myeloid cells in axonal regeneration was assessed using axonal injury models and CD11b-TKmt-30 mice expressing a mutated HSV-1 thymidine kinase (TK) gene regulated by the myeloid-specific CD11b promoter. Continuous delivery of ganciclovir at a sciatic nerve lesion site greatly decreased the number of granulocytes/inflammatory monocytes and macrophages in the distal stump of CD11b-TKmt-30 mice. Axonal regeneration and locomotor function recovery were severely compromised in ganciclovir-treated CD11b-TKmt-30 mice. This was caused by an unsuitable growth environment rather than an altered regeneration capacity of neurons. In absence of CD11b(+) cells, the clearance of inhibitory myelin debris was prevented, neurotrophin synthesis was abolished, and blood vessel formation/ maintenance was severely compromised in the sciatic nerve distal stump. Spinal cord-injured axons also failed to regenerate through peripheral nerve grafts in the absence of CD11b(+) cells. Therefore, myeloid cells support axonal regeneration and functional recovery by creating a growth-permissive milieu for injured axons.