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Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2000, Vol. 96, No. 6, pp. 2157-2162 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Contribution of ecto-5'-nucleotidase to the inhibition of platelet aggregation by human endothelial cells Yasuko Kawashima, Toshiro Nagasawa, and Haruhiko Ninomiya From the Division of Hematology, the Institute of Clinical Medicine, and the College of Medical Technology, University of Tsukuba, Tsukuba, Ibaraki, Japan. We studied the role of adenosine (Ado), which is generated from adenine nucleotides via the activity of ecto-5'-nucleotidase (ecto-5'-NT), in the inhibition of platelet aggregation by endothelial cells (ECs). The enzymatic activity of nucleotidases on human umbilical vein endothelial cells (HUVECs) was examined with regard to (1) the inhibition of adenosine diphosphate (ADP)-induced platelet aggregation and (2) the liberation of inorganic phosphate from adenine nucleotides. Adenosine 5'-monophosphate (AMP) preincubated with HUVECs significantly inhibited ADP-induced platelet aggregation. This was completely blocked by the treatment of HUVECs with a specific inhibitor of ecto-5'-NT, 5'-[-methylene] diphosphate (APCP), or by the addition of an A2a receptor antagonist. Neither nitric oxide nor prostacyclin was involved in this inhibitory activity, suggesting that Ado generated in the incubation medium by the activity of 5'-NT on HUVECs inhibited platelet aggregation. When ADP was incubated on HUVECs, it lost most of its agonistic activity for platelets. Pretreatment of HUVECs with APCP at a concentration that abolished ecto-5'-NT activity partially restored ADP-induced platelet aggregation. Ecto-5'-NT contributes to EC function by inhibiting platelet aggregation in cooperation with ATP diphosphohydrolase, which degrades ADP to AMP. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Huang, D. J. Moore, R. J. Ketchum, C. S. Nunemaker, B. Kovatchev, A. L. McCall, and K. L. Brayman Resolving the Conundrum of Islet Transplantation by Linking Metabolic Dysregulation, Inflammation, and Immune Regulation Endocr. Rev., August 1, 2008; 29(5): 603 - 630. [Abstract] [Full Text] [PDF] M. L. Hart, D. Kohler, T. Eckle, D. Kloor, G. L. Stahl, and H. K. Eltzschig Direct Treatment of Mouse or Human Blood With Soluble 5'-Nucleotidase Inhibits Platelet Aggregation Arterioscler Thromb Vasc Biol, August 1, 2008; 28(8): 1477 - 1483. [Abstract] [Full Text] [PDF] P. Koszalka, B. Ozuyaman, Y. Huo, A. Zernecke, U. Flogel, N. Braun, A. Buchheiser, U. K.M. Decking, M. 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