VEGFR-1 Signaling Regulates the Homing of Bone Marrow-Derived Cells in a Mouse Stroke Model
VEGFR-1 Signaling Regulates the Homing of Bone Marrow-Derived Cells in a Mouse Stroke Model
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DOI：
10.1097/nen.0b013e3181c9c05b
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发表时间：
2010-02-01
影响因子：
3.2
通讯作者：
Plate, Karl H.
中科院分区：
文献类型：
--
作者：
Beck, Heike;Raab, Sabine;Plate, Karl H.
血管内皮生长因子受体I(VEGFR-1)在血管内皮细胞中高表达，通过作为诱饵受体和捕获血管内皮生长因子-A来调节发育中的血管生成。血管内皮生长因子受体I在单核细胞和巨噬细胞中也有表达；缺乏VEGFR-I酪氨酸激酶(TK)结构域(VEGFR-1 TK-/-鼠)的小鼠表现出巨噬细胞功能受损。因为巨噬细胞被招募到脑缺血梗塞的部位，我们假设骨髓(BM)细胞中缺乏VEGFR-I TK会影响实验性中风模型的结果。以VEGFR-1 TK+/+和VEGFR-1 TK-/-小鼠为供体，对C57BL/6J小鼠进行了骨髓移植实验，并分析了脑缺血后细胞的浸润情况。在缺血后3天，VEGFR-I、TK-/-髓系细胞向梗塞组织的初始募集减少，缺血后血管生成减少。10天时，两组梗死灶周围区的浸润性细胞数和血管密度基本相同。缺血后3天和10天的脑梗塞面积和24小时的神经功能评分在两组间均无差异。这些结果支持VEGFR-I信号在脑缺血后骨髓浸润和血管生成的早期调节中的作用。
Vascular endothelial growth factor receptor I (VEGFR-1) is highly expressed in endothelial cells and regulates developmental angiogenesis by acting as a decoy receptor and trapping VEGF-A. Vascular endothelial growth factor receptor I is also expressed in monocytes and macrophages; mice lacking the VEGFR-I tyrosine kinase (TK) domain (VEGFR-1 TK-/- mice) display impaired macrophage function. Because macrophages are recruited to sites of cerebral ischemic infarcts, we hypothesized that lack of VEGFR-I TK in bone marrow (BM) cells would affect the outcome in an experimental stroke model. We performed BM transplantation experiments in C57BL/6J mice using VEGFR-1 TK+/+ and VEGFR-1 TK-/- mice as BM donors and analyzed cell infiltration after cerebral ischemia. There was reduced initial recruitment of VEGFR-I TK-/- myeloid cells into the infarcted tissue and reduced postischemic angiogenesis at 3 days postischemia. By 10 days, the numbers of infiltrating cells and the densities of vessels in the infarct peri-infarct zone were similar for both groups. Neither infarct size at 3 and 10 days postischemia nor neurological performance at 24 hours was different between the experimental groups. These results support a role of VEGFR-I signaling in the early regulation of BM infiltration and angiogenesis after brain ischemia.