Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4

Neurobiology of Disease

Pia M. Vidal¹  Dearbhaile Dooley¹  Martin Metz¹  Leen Willems¹  Lies Geboes¹  Tim Vangansewinkel¹  Gunnar Pejler¹  Nathalie Geurts²  Marcus Maurer²  Francesco Boato²  Stefanie Lemmens²  Evi Lemmens²  Sofie Nelissen²  Debora Pehl²  Sven Hendrix² 

[1] Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium;;Dept. of Morphology &

关键词: mMCP4;    Mast cell;    Inflammation;    Spinal cord injury;    MCP-1;    TNF-α;   

DOI  :  

来源: DOAJ

【 摘 要 】

Mast cells (MCs) are found abundantly in the central nervous system and play a complex role in neuroinflammatory diseases such as multiple sclerosis and stroke. In the present study, we show that MC-deficient KitW-sh/W-sh mice display significantly increased astrogliosis and T cell infiltration as well as significantly reduced functional recovery after spinal cord injury compared to wildtype mice. In addition, MC-deficient mice show significantly increased levels of MCP-1, TNF-α, IL-10 and IL-13 protein levels in the spinal cord. Mice deficient in mouse mast cell protease 4 (mMCP4), an MC-specific chymase, also showed increased MCP-1, IL-6 and IL-13 protein levels in spinal cord samples and a decreased functional outcome after spinal cord injury. A degradation assay using supernatant from MCs derived from either mMCP4−/− mice or controls revealed that mMCP4 cleaves MCP-1, IL-6, and IL-13 suggesting a protective role for MC proteases in neuroinflammation. These data show for the first time that MCs may be protective after spinal cord injury and that they may reduce CNS damage by degrading inflammation-associated cytokines via the MC-specific chymase mMCP4.

【 授权许可】

Unknown