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Research article2014Peer reviewedOpen access

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

Nelissen, Sofie; Vangansewinkel, Tim; Geurts, Natalie; Geboes, Lies; Lemmens, Evi; Vidal, Pia M.; Lemmens, Stefanie; Willems, Leen; Boato, Francesco; Dooley, Dearbhaile; Pehl, Debora; Pejler, Gunnar; Maurer, Markus; Metz, Martin; Hendrix, Sven

Abstract

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 Kit(W-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-alpha, 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 cytoldnes via the MC-specific chymase mMCP4. (C) 2013 The Authors. Published by Elsevier Inc All rights reserved.

Keywords

mMCP4; Mast cell; Inflammation; Spinal cord injury; MCP-1; TNF-alpha; IL-6; IL-10; IL-13

Published in

Neurobiology of Disease
2014, Volume: 62, pages: 260-272
Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE

    UKÄ Subject classification

    Immunology in the medical area
    Neurosciences

    Publication identifier

    DOI: https://doi.org/10.1016/j.nbd.2013.09.012

    Permanent link to this page (URI)

    https://res.slu.se/id/publ/52769