| الوصف: |
Microglia and macrophage mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage (ICH). Dynamic cytoskeletal changes accompany phagocytosis; however, whether and how they are associated with microglia/macrophages mediated erythrophagocytosis remain unclear. In this study, we investigated the dynamics of microtubule cytoskeleton in microglia/macrophage erythrophagocytosis after ICH both in vitro and in vivo. We first assessed the function of acetylated α-tubulin (Ac α-tub), a stabilized microtubule form, in erythrophagocytosis in primary DiO GFP-labeled red blood cells (RBCs) co-cultured with microglia cell line BV2 or macrophage cell line RAW264.7. Intriguingly, the expression of Ac α-tub was significantly decreased in BV2 and RAW264.7 cells with erythrophagocytosis. Moreover, silencing ATAT1, a newly discovered α-tubulin acetyltransferase, decreased ATAT1 levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells. Consistently, in ATAT1−/− mice, we observed increased Iba-1 and perls positive microglia/macrophage phagocytes of RBCs in peri-hematoma and reduced hematoma volume in mice with ICH. Additionally, knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines, as well as increasing anti-inflammatory cytokines around hematoma, and ultimately improved neurological recovery of after ICH. In conclusion, ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophage and hematoma absorption after ICH. These results provided novel insights into the mechanisms of hematoma clearance and the identification of therapeutic target for treating ICH. |
