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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/14980

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
Citation: 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.
URI: http://hdl.handle.net/1942/14980
DOI: 10.1096/fj.12-204800
ISI #: 000315585200008
ISSN: 0892-6638
Category: A1
Type: Journal Contribution
Validation: ecoom, 2014
Appears in Collections: Research publications

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