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

Fan-Qi Kong,Hao Liu,Peng Sun,Chang-Jiang Gu,Ye Zhu,Han-Wen Zhang,Shu-Jie Zhao,Jian Chen,Jin Fan,Ding-Fei Qian,An-Di Xu,Tao Xu,Guo-Yong Yin,Jian Jie,Qi Chen,Zheng Zhou,Ya-Qing Yang

doi:10.1186/s12974-020-01735-2

Abstract

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-κB 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.

Highlights

A sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery
macrophage scavenger receptor 1 (MSR1) deficiency improved functional recovery and reduced cellular damage after spinal cord injury To investigate the role of MSR1 in the pathophysiology of SCI, quantitative PCR and western blot analysis were used to confirm its expression pattern in the lesion site at 3, 7, and 14 days post injury
Compared with those in the sham operation group, the mRNA and protein levels of MSR1 were significantly upregulated in the SCI group, with the peak of expression observed on day 7 (Fig. 1a–c)

Summary

Introduction

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. The initial mechanical trauma usually triggers a secondary damage cascade, where a sustained inflammatory response to the secondary injury could contribute to neuronal apoptosis, demyelination, and. As the main immune cells, macrophages are recruited to the lesion epicenter at 2–3 days after the SCI and play important roles in the secondary injury [8]. Zhu et al further indicated that the transcription profile of macrophages most resembles that of foam cells that reside in atherosclerotic plaques at day 7 post injury [13]. The myelin debris resulting from continuous demyelination contributes to the formation of foamy

Methods

Results

Discussion

Conclusion