Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4
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 w...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-02-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996113002581 |
| id |
doaj-c4ea801aa65d481681b4c71e2b849fbb |
|---|---|
| record_format |
Article |
| spelling |
doaj-c4ea801aa65d481681b4c71e2b849fbb2021-03-22T12:40:25ZengElsevierNeurobiology of Disease1095-953X2014-02-0162260272Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4Sofie Nelissen0Tim Vangansewinkel1Nathalie Geurts2Lies Geboes3Evi Lemmens4Pia M. Vidal5Stefanie Lemmens6Leen Willems7Francesco Boato8Dearbhaile Dooley9Debora Pehl10Gunnar Pejler11Marcus Maurer12Martin Metz13Sven Hendrix14Dept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, BelgiumDept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, BelgiumDept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, BelgiumDept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, BelgiumDept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, BelgiumDept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, BelgiumDept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, BelgiumDept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, BelgiumDept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, BelgiumDept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, BelgiumDept. of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, GermanyDept. of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, SwedenDept. of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, GermanyDept. of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, GermanyDept. of Morphology & Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium; Corresponding author at: Dept. of Morphology & Biomedical Research Institute, Martelarenlaan 42, Hasselt, Diepenbeek 3500, Belgium. Fax: +32 11 26 9299.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.http://www.sciencedirect.com/science/article/pii/S0969996113002581mMCP4Mast cellInflammationSpinal cord injuryMCP-1TNF-α |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Sofie Nelissen Tim Vangansewinkel Nathalie Geurts Lies Geboes Evi Lemmens Pia M. Vidal Stefanie Lemmens Leen Willems Francesco Boato Dearbhaile Dooley Debora Pehl Gunnar Pejler Marcus Maurer Martin Metz Sven Hendrix |
| spellingShingle |
Sofie Nelissen Tim Vangansewinkel Nathalie Geurts Lies Geboes Evi Lemmens Pia M. Vidal Stefanie Lemmens Leen Willems Francesco Boato Dearbhaile Dooley Debora Pehl Gunnar Pejler Marcus Maurer Martin Metz Sven Hendrix 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 mMCP4 Mast cell Inflammation Spinal cord injury MCP-1 TNF-α |
| author_facet |
Sofie Nelissen Tim Vangansewinkel Nathalie Geurts Lies Geboes Evi Lemmens Pia M. Vidal Stefanie Lemmens Leen Willems Francesco Boato Dearbhaile Dooley Debora Pehl Gunnar Pejler Marcus Maurer Martin Metz Sven Hendrix |
| author_sort |
Sofie Nelissen |
| title |
Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4 |
| title_short |
Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4 |
| title_full |
Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4 |
| title_fullStr |
Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4 |
| title_full_unstemmed |
Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4 |
| title_sort |
mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4 |
| publisher |
Elsevier |
| series |
Neurobiology of Disease |
| issn |
1095-953X |
| publishDate |
2014-02-01 |
| description |
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. |
| topic |
mMCP4 Mast cell Inflammation Spinal cord injury MCP-1 TNF-α |
| url |
http://www.sciencedirect.com/science/article/pii/S0969996113002581 |
| work_keys_str_mv |
AT sofienelissen mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT timvangansewinkel mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT nathaliegeurts mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT liesgeboes mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT evilemmens mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT piamvidal mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT stefanielemmens mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT leenwillems mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT francescoboato mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT dearbhailedooley mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT deborapehl mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT gunnarpejler mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT marcusmaurer mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT martinmetz mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 AT svenhendrix mastcellsprotectfromposttraumaticspinalcorddamageinmicebydegradinginflammationassociatedcytokinesviamousemastcellprotease4 |
| _version_ |
1724208391745699840 |