The endothelial cell ecto-ADPase responsible for inhibition of platelet function is CD39
The endothelial cell ecto-ADPase responsible for inhibition of platelet function is CD39
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DOI：
10.1172/jci119294
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发表时间：
1997-03-15
影响因子：
15.9
通讯作者：
Maliszewski, CR
中科院分区：
文献类型：
--
作者：
Marcus, AJ;Broekman, MJ;Maliszewski, CR
我们以前曾证明，当血小板处于运动状态并接近内皮细胞时，它们对激动剂(Marcus，A.J.，L.B.Safier，K.A.Hajjar，H.L.Ullman，N.伊斯拉姆，M.J.Broekman和A.M.Eiroa)变得没有反应。1991年。J·克莱恩。投资。88：1690-1696)。这种抑制是由于内皮细胞表面的胞外ADPase代谢激活的血小板释放的ADP，导致聚集反应被阻断。人脐静脉内皮细胞(HUVEC)ADPase生化分类为E-型ATP-二磷酸水解酶。内皮细胞胞外ADPase在这里被确认为CD39，一种最初被描述为淋巴表面抗原的分子。人脐静脉内皮细胞胞外ADPase活性均由抗CD39的单抗免疫沉淀。通过共聚焦显微镜和流式细胞仪分析建立人脐静脉内皮细胞CD39的表面定位。将人CD39导入COS细胞后，CD39的胞外ADPase活性和表面表达均增强。从人脐静脉内皮细胞和重组人CD39中扩增出大小相同、序列相同的产物。Northern印迹分析表明，HUVEC表达与MP-1细胞(最初克隆CD39的细胞)相同大小的CD39转录本。我们通过证明CD39转基因的COS细胞获得了抑制ADP诱导的富含血小板的血浆中聚集的能力，从而确立了CD39作为主要的内皮血栓调节因子的作用。HUVEC ADPase/CD39是一种结构性表达的有效的血小板反应性抑制因子，为抗血栓治疗提供了新的前景。
We previously demonstrated that when platelets are in motion and in proximity to endothelial cells, they become unresponsive to agonists (Marcus, A.J., L.B. Safier, K.A. Hajjar, H.L. Ullman, N. Islam, M.J. Broekman, and A.M. Eiroa. 1991. J. Clin. Invest. 88:1690-1696). This inhibition is due to an ecto-ADPase on the surface of endothelial cells which metabolizes ADP released from activated platelets, resulting in blockade of the aggregation response. Human umbilical vein endothelial cells (HUVEC) ADPase was biochemically classified as an E-type ATP-diphosphohydrolase. The endothelial ecto-ADPase is herein identified as CD39, a molecule originally characterized as a lymphoid surface antigen. All HUVEC ecto-ADPase activity was immunoprecipitated by monoclonal antibodies to CD39. Surface localization of HUVEC CD39 was established by confocal microscopy and flow cytometric analyses. Transfection of COS cells with human CD39 resulted in both ecto-ADPase activity as well as surface expression of CD39. PCR analyses of cDNA obtained from HUVEC mRNA and recombinant human CD39 revealed products of the same size, and of identical sequence. Northern blot analyses demonstrated that HUVEC express the same sized transcripts for CD39 as MP-1 cells (from which CD39 was originally cloned). We established the role of CD39 as a prime endothelial thromboregulator by demonstrating that CD39-transfected COS cells acquired the ability to inhibit ADP-induced aggregation in platelet-rich plasma. The identification of HUVEC ADPase/CD39 as a constitutively expressed potent inhibitor of platelet reactivity offers new prospects for antithrombotic therapeusis.