http://www.fasebj.org/content/early/2012/11/26/fj.12-204800.abstract
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 KitW/KitW-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 KitW-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.
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