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. Findings: 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-κB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons. Interpretation: 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. Funding Statement: This study was supported by grants from the National Natural Science Foundation of China (81772351, 81520108018, 81472080, 81772352, and 81401800), the Jiangsu Committee of Science and Technology–Social Development Plan (BE2017755), the Jiangsu Six Talents Peak (WSN-011), the Nanjing Committee of Science and Technology (201505005), Medical Science and technology development Foundation from Nanjing Department of Health (YKK17060), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX18_0430). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The animal protocols were approved by the Animal Committee of the First Affiliated Hospital of Nanjing Medical University.