ASTROCYTES ARE THE PRIMARY SOURCE OF TISSUE FACTOR IN THE MURINE CENTRAL-NERVOUS-SYSTEM - A ROLE FOR ASTROCYTES IN CEREBRAL HEMOSTASIS
ASTROCYTES ARE THE PRIMARY SOURCE OF TISSUE FACTOR IN THE MURINE CENTRAL-NERVOUS-SYSTEM - A ROLE FOR ASTROCYTES IN CEREBRAL HEMOSTASIS
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DOI：
10.1172/jci116573
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发表时间：
1993-07-01
影响因子：
15.9
通讯作者：
MACKMAN, N
中科院分区：
文献类型：
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作者：
EDDLESTON, M;DELATORRE, JC;MACKMAN, N
脑内止血至关重要，因为出血进入神经实质可导致瘫痪、昏迷和死亡。与这种对出血的敏感性相一致，脑中含有大量的组织因子（TF），这是凝血蛋白酶级联反应的主要细胞引发剂。然而，迄今为止，TF在中枢神经系统中的细胞来源尚未确定。在这项研究中，通过原位杂交对小鼠脑切片的分析表明，在表达胶质细胞酸性蛋白（星形胶质细胞的特异性标志物）的细胞中存在高水平的TF mRNA。此外，原代小鼠星形胶质细胞培养物和小鼠、大鼠和人星形胶质细胞系组成型表达TF mRNA和功能蛋白。这些数据表明，星形胶质细胞是TF在中枢神经系统中的主要来源。我们认为，星形胶质细胞形成神经血管周围和深入脑膜的胶质界膜密切参与控制脑出血。最后，我们观察到羊瘙痒病感染小鼠脑中TF mRNA表达增加。在没有出血的情况下TF表达的这种调节表明TF可能通过改变正常和患病脑中蛋白酶的产生而在止血以外的过程中起作用。
Hemostasis in the brain is of paramount importance because bleeding into the neural parenchyma can result in paralysis, coma, and death. Consistent with this sensitivity to hemorrhage, the brain contains large amounts of tissue factor (TF), the major cellular initiator of the coagulation protease cascades. However, to date, the cellular source for TF in the central nervous system has not been identified. In this study, analysis of murine brain sections by in situ hybridization demonstrated high levels of TF mRNA in cells that expressed glial fibrillary acidic protein, a specific marker for astrocytes. Furthermore, primary mouse astrocyte cultures and astrocvte cell lines from mouse, rat, and human constitutively expressed TF mRNA and functional protein. These data indicated that astrocytes are the primary source of TF in the central nervous system. We propose that astrocytes forming the glia limitans around the neural vasculature and deep to the meninges are intimately involved in controlling hemorrhage in the brain. Finally, we observed an increase in TF mRNA expression in the brains of scrapie-infected mice. This modulation of TF expression in the absence of hemorrhage suggested that TF may function in processes other than hemostasis by altering protease generation in normal and diseased brain.