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Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury.


ABSTRACT: BACKGROUND:A 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. METHODS:The 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. RESULTS:In 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-?B signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons. CONCLUSIONS:Our 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.

SUBMITTER: Kong FQ 

PROVIDER: S-EPMC7027125 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury.

Kong Fan-Qi FQ   Zhao Shu-Jie SJ   Sun Peng P   Liu Hao H   Jie Jian J   Xu Tao T   Xu An-Di AD   Yang Ya-Qing YQ   Zhu Ye Y   Chen Jian J   Zhou Zheng Z   Qian Ding-Fei DF   Gu Chang-Jiang CJ   Chen Qi Q   Yin Guo-Yong GY   Zhang Han-Wen HW   Fan Jin J  

Journal of neuroinflammation 20200217 1


<h4>Background</h4>A 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 p  ...[more]

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