Xing Changhong, Lee Sunryung, Kim Woo Jean, Wang Hui, Yang Yong-Guang, Ning MingMing, Wang Xiaoying, Lo Eng H
Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
J Neurosci Res. 2009 Aug 15;87(11):2571-7. doi: 10.1002/jnr.22076.
The concept of the neurovascular unit emphasizes that common signals and substrates underlie the physiology and pathophysiology of neuronal and endothelial compartments in brain. Recent data suggest that activation of the integrin-associated protein CD47 promotes neuronal cell death. Is it possible that CD47 may also negatively affect cerebral endothelial cells? Exposure of wild-type primary mouse cerebral endothelial cells to the CD47 ligand thrombospondin 1 (TSP-1) induced an increasing amount of cell death, whereas cytotoxicity was significantly decreased in cerebral endothelial cells derived from CD47 knockout mice. The specific CD47-activating peptide, 4N1K, similarly induced cell death in human brain microvascular endothelial cells. Promotion of inflammation was also involved because lower TSP-1 was able to up-regulate the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Finally, CD47 signaling may suppress angiogenesis because 4N1K significantly inhibited endothelial cell migration and tube formation in vitro. We conclude that CD47 signaling can negatively affect the viability and function of cerebral endothelial cells, further supporting the notion that CD47 may be a potential neurovascular target for stroke and brain injury.
神经血管单元的概念强调，共同的信号和底物是大脑中神经元和内皮细胞区室生理和病理生理的基础。最近的数据表明，整合素相关蛋白CD47的激活会促进神经元细胞死亡。CD47是否也可能对脑内皮细胞产生负面影响呢？将野生型原代小鼠脑内皮细胞暴露于CD47配体血小板反应蛋白1（TSP-1）会导致细胞死亡数量增加，而在源自CD47基因敲除小鼠的脑内皮细胞中，细胞毒性则显著降低。特异性CD47激活肽4N1K同样会诱导人脑微血管内皮细胞死亡。炎症的促进也与之相关，因为较低浓度的TSP-1能够上调细胞间黏附分子-1和血管细胞黏附分子-1等黏附分子。最后，CD47信号可能会抑制血管生成，因为4N1K在体外显著抑制了内皮细胞迁移和管腔形成。我们得出结论，CD47信号可对脑内皮细胞的活力和功能产生负面影响，进一步支持了CD47可能是中风和脑损伤潜在神经血管靶点的观点。
