Assignment of ecto-nucleoside triphosphate diphosphohydrolase-1/cd39 expression to microglia and vasculature of the brain
Assignment of ecto-nucleoside triphosphate diphosphohydrolase-1/cd39 expression to microglia and vasculature of the brain
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DOI：
10.1111/j.1460-9568.2000.01342.x
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发表时间：
2000-12-01
影响因子：
3.4
通讯作者：
Zimmermann, H
中科院分区：
文献类型：
--
作者：
Braun, N;Sévigny, J;Zimmermann, H
细胞外核苷酸是一种普遍存在的细胞外介质，与P2受体相互作用并激活。这些受体启动了各种各样的信号通路，这些通路似乎对神经元和神经胶质细胞之间的功能联系以及对大脑中的血流、止血和炎症反应的调节都很重要。胞外核苷酸酶是一种细胞外核苷酸代谢酶，通过调节这些激动剂的水解来调节P2受体介导的信号转导。已经描述了相当数量的胞外酶种类，它们的底物和组织分布部分重叠。在大脑中表达的主要候选者是外核苷三磷酸二磷酸水解酶(E-NTPDase或CD39)家族的成员。CD39(-/-)小鼠和特异性试剂的产生使我们能够分析酶家族的原型成员NTPDase1(CD39)在小鼠脑中的特定细胞分布。利用单特异性抗体和酶组织化学染色，我们已经确定NTPDase1是一种与小胶质细胞以及血管内皮细胞和平滑肌细胞相关的主要胞外核苷酸酶。NTPDase1在神经元和星形胶质细胞中不表达。在整个脑实质观察到更低水平的其他未知的外源核糖核酸酶功能活性。NTPDase1可能调节P2受体介导的小胶质细胞功能，并影响神经元或星形胶质细胞之间的核苷酸信号转导，这与多个小胶质细胞分支有关。脑血管内皮细胞和血管平滑肌细胞NTPDase1的表达也提示它参与了血流调节和血栓形成。
Extracellular nucleotides are ubiquitous extracellular mediators that interact with and activate nucleotide type 2 (P2) receptors. These receptors initiate a wide variety of signalling pathways that appear important for functional associations between neurons and glial cells and for the regulation of blood flow, haemostatic and inflammatory reactions in the brain. Ectonucleotidases are extracellular nucleotide-metabolizing enzymes that modulate P2 receptor-mediated signalling by the regulated hydrolysis of these agonists. A considerable number of ectoenzyme species with partially overlapping substrate and tissue distributions have been described. Major candidates for expression in the brain are members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase or CD39) family. The production of cd39(-/-) mice and specific reagents have enabled us to analyse the specific cellular distribution of NTPDase1 (CD39), the prototype member of the enzyme family, in the mouse brain. Using monospecific antibodies and enzyme histochemical staining, we have identified NTPDase1 as a major ectonucleotidase associated with both microglia and the endothelial and smooth muscle cells of the vasculature. NTPDase1 is not expressed by neurons and astrocytes. Additional unidentified ectonucleotidase functional activity is observed at lower levels throughout the brain parenchyma. NTPDase1 may regulate P2 receptor-mediated functions of microglia as well as influence nucleotide signalling between neurons or astrocytes that are associated with multiple microglial ramifications. The expression of NTPDase1 by cerebrovascular endothelial and smooth muscle cells also suggests involvement in the regulation of blood flow and thrombogenesis.