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Title: | Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4 | Authors: | HENDRIX, Sven Kramer, Peter Pehl, Debora Warnke, Katharina Boato, Francesco NELISSEN, Sofie LEMMENS, Evi Pejler, Gunnar Metz, Martin Siebenhaar, Frank Maurer, Marcus |
Issue Date: | 2013 | Publisher: | FEDERATION AMER SOC EXP BIOL | Source: | FASEB JOURNAL, 27 (3), p. 920-929 | Abstract: | Mast cells (MCs) are found abundantly in the brain and the meninges and play a complex role in neuroinflammatory diseases, such as stroke and multiple sclerosis. Here, we show that MC-deficient Kit(W)/Kit(W-v) mice display increased neurodegeneration in the lesion area after brain trauma. Furthermore, MC-deficient mice display significantly more brain inflammation, namely an increased presence of macrophages/microglia, as well as dramatically increased T-cell infiltration at days 4 and 14 after injury, combined with increased astrogliosis at day 14 following injury. The number of proliferating Ki67(+) macrophages/microglia and astrocytes around the lesion area is more than doubled in these MC-deficient mice. In parallel, MC-deficient Kit(W-sh/W-sh) mice display increased presence of macrophages/microglia at day 4, and persistent astrogliosis at day 4 and 14 after brain trauma. Further analysis of mice deficient in one of the most relevant MC proteases, i.e., mouse mast cell protease 4 (mMCP-4), revealed that astrogliosis and T-cell infiltration are significantly increased in mMCP-4-knockout mice. Finally, treatment with an inhibitor of mMCP-4 significantly increased macrophage/microglia numbers and astrogliosis. These data suggest that MCs exert protective functions after trauma, at least in part via mMCP-4, by suppressing exacerbated inflammation via their proteases.-Hendrix, S., Kramer, P., Pehl, D., Warnke, K., Boato, F., Nelissen, S., Lemmens, E., Pejler, G., Metz, M., Siebenhaar, F., Maurer, M. Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4. FASEB J. 27, 920-929 (2013). www.fasebj.org | Notes: | [Hendrix, Sven; Boato, Francesco; Nelissen, Sofie; Lemmens, Evi] Hasselt Univ, Dept Morphol, Diepenbeek, Belgium. [Hendrix, Sven; Boato, Francesco; Nelissen, Sofie; Lemmens, Evi] Hasselt Univ, Biomed Res Inst, Diepenbeek, Belgium. [Kramer, Peter; Pehl, Debora; Warnke, Katharina] Charite, Ctr Anat Cell Biol & Neurobiol, D-13353 Berlin, Germany. [Metz, Martin; Siebenhaar, Frank; Maurer, Marcus] Charite, Dept Dermatol, D-13353 Berlin, Germany. [Pejler, Gunnar] Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden. | Keywords: | entorhinal cortex lesion; mMCP-4; protease; T cells;Biochemistry & Molecular Biology; Biology; Cell Biology; entorhenal cortex lesion; mMCP-4; protease; T cells | Document URI: | http://hdl.handle.net/1942/14980 | ISSN: | 0892-6638 | e-ISSN: | 1530-6860 | DOI: | 10.1096/fj.12-204800 | ISI #: | 000315585200008 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2014 |
Appears in Collections: | Research publications |
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