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.
A J Marcus, M J Broekman, J H Drosopoulos, N Islam, T N Alyonycheva, L B Safier, K A Hajjar, D N Posnett, M A Schoenborn, K A Schooley, R B Gayle, C R Maliszewski
Title and authors | Publication | Year |
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Delayed targeting of CD39 to activated platelet GPIIb/IIIa via a single-chain antibody: breaking the link between antithrombotic potency and bleeding?
JD Hohmann, X Wang, S Krajewski, C Selan, CA Haller, A Straub, EL Chaikof, HH Nandurkar, CE Hagemeyer, K Peter |
Blood | 2013 |
Harnessing the Platelet Signaling Network to Produce an Optimal Hemostatic Response
LF Brass, M Tomaiuolo, TJ Stalker |
Hematology/Oncology Clinics of North America | 2013 |
Regulation of ecto-apyrase CD39 (ENTPD1) expression by phosphodiesterase III (PDE3)
AE Baek, Y Kanthi, NR Sutton, H Liao, DJ Pinsky |
The FASEB Journal | 2013 |
Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating
PH Nilsson, KN Ekdahl, PU Magnusson, H Qu, H Iwata, D Ricklin, J Hong, JD Lambris, B Nilsson, Y Teramura |
Biomaterials | 2013 |
Crosstalk between ER stress and immunogenic cell death
O Kepp, L Menger, E Vacchelli, C Locher, S Adjemian, T Yamazaki, I Martins, AQ Sukkurwala, M Michaud, L Senovilla, L Galluzzi, G Kroemer, L Zitvogel |
Cytokine & Growth Factor Reviews | 2013 |
Antithrombotic effect of repeated doses of the ethanolic extract of local olive ( Olea europaea L.) leaves in rabbits
AM Dub, AM Dugani |
The Libyan journal of medicine | 2013 |
Endothelialization of implanted cardiovascular biomaterial surfaces: The development from in vitro to in vivo: Endothelialization of Implanted Cardiovascular Biomaterial Surfaces
T Liu, S Liu, K Zhang, J Chen, N Huang |
Journal of biomedical materials research. Part A | 2013 |
Hydrolysis of extracellular ATP by ectonucleoside triphosphate diphosphohydrolase (ENTPD) establishes the set point for fibrotic activity of cardiac fibroblasts
D Lu, PA Insel |
The Journal of biological chemistry | 2013 |
Antithrombotic effect of repeated doses of the ethanolic extract of local olive (Olea europaea L.) leaves in rabbits
AM Dub, AM Dugani |
Libyan Journal of Medicine | 2013 |
Molecular Basis of Purinergic Signal Metabolism by Ectonucleotide Pyrophosphatase/Phosphodiesterases 4 and 1 and Implications in Stroke
RA Albright, DL Ornstein, W Cao, WC Chang, D Robert, M Tehan, D Hoyer, L Liu, P Stabach, G Yang, EM de la Cruz, DT Braddock |
The Journal of biological chemistry | 2013 |
Omics for Personalized Medicine
D Barh, D Dhawan, NK Ganguly |
2013 | |
Stress Signaling in Plants: Genomics and Proteomics Perspective, Volume 1
M Sarwat, A Ahmad, MZ Abdin |
2013 |