Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury
Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury
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DOI：
10.1186/s12974-020-01735-2
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发表时间：
2020-02-17
影响因子：
9.3
通讯作者：
Fan, Jin
中科院分区：
文献类型：
--
作者：
Kong, Fan-Qi;Zhao, Shu-Jie;Fan, Jin
脊髓损伤（SCI）后持续的炎症反应导致神经元损伤，抑制功能恢复。巨噬细胞是炎症反应的主要参与者，吞噬髓磷脂碎片后转化为泡沫状巨噬细胞，释放炎症因子，放大继发性损伤。在此，我们评估了巨噬细胞清除率受体1 （MSR1）在脊髓损伤后髓鞘碎片吞噬中的作用，并解释了其可能的机制。方法采用脊髓损伤模型，测定MSR1在体内吞噬髓磷脂碎片中的关键作用。在体外用髓磷脂碎片处理巨噬细胞和RAW264.7后，采用qPCR、western blotting和免疫荧光技术探索MSR1的潜在功能和机制。结果在本研究中，我们发现MSR1基因敲除小鼠的创伤性脊髓损伤恢复优于MSR1野生型小鼠。此外，MSR1促进髓磷脂碎片的吞噬和泡沫巨噬细胞的形成，导致体外和体内的促炎极化。机制上，在髓磷脂碎片存在下，msr1介导的NF-kappa B信号通路促进了炎症介质的释放和随后的神经元凋亡。结论sour研究阐明了先前未被认识的MSR1在脊髓损伤病理生理中的作用，并提示其抑制可能是这种创伤性疾病的一种新的治疗策略。
BackgroundA sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery. Macrophages, the major participants in the inflammatory response, transform into foamy macrophages after phagocytosing myelin debris, subsequently releasing inflammatory factors and amplifying the secondary injury. Here, we assessed the effect of macrophage scavenger receptor 1 (MSR1) in phagocytosis of myelin debris after SCI and explained its possible mechanism.MethodsThe SCI model was employed to determine the critical role of MSR1 in phagocytosis of myelin debris in vivo. The potential functions and mechanisms of MSR1 were explored using qPCR, western blotting, and immunofluorescence after treating macrophages and RAW264.7 with myelin debris in vitro.ResultsIn this study, we found improved recovery from traumatic SCI in MSR1-knockout mice over that in MSR1 wild-type mice. Furthermore, MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization in vitro and in vivo. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-kappa B signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons.ConclusionsOur study elucidates a previously unrecognized role of MSR1 in the pathophysiology of SCI and suggests that its inhibition may be a new treatment strategy for this traumatic condition.