| First Author | Hendrix S | Year | 2013 |
| Journal | FASEB J | Volume | 27 |
| Issue | 3 | Pages | 920-9 |
| PubMed ID | 23193170 | Mgi Jnum | J:196981 |
| Mgi Id | MGI:5490422 | Doi | 10.1096/fj.12-204800 |
| Citation | Hendrix S, et al. (2013) Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4. FASEB J 27(3):920-9 |
| abstractText | 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. |
