title: Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4.
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/Kit 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 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.
authors.affiliation: Department of Morphology and Biomedical Research Institute, Agoralaan Gebouw D, BE 3590 Diepenbeek, Belgium. sven.hendrix@uhasselt.be
authors.forename: Sven
authors.initials: S
authors.lastname: Hendrix
authors.forename: Peter
authors.initials: P
authors.lastname: Kramer
authors.forename: Debora
authors.initials: D
authors.lastname: Pehl
authors.forename: Katharina
authors.initials: K
authors.lastname: Warnke
authors.forename: Francesco
authors.initials: F
authors.lastname: Boato
authors.forename: Sofie
authors.initials: S
authors.lastname: Nelissen
authors.forename: Evi
authors.initials: E
authors.lastname: Lemmens
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
authors.forename: Martin
authors.initials: M
authors.lastname: Metz
authors.forename: Frank
authors.initials: F
authors.lastname: Siebenhaar
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D053818:Chymases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D009419:Nerve Tissue Proteins; D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases; C066932:mast cell protease 4; D053818:Chymases