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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Contribution of E-NTPDase1 (CD39) to renal protection from ischemia-reperfusion injury
A Grenz, H Zhang, M Hermes, T Eckle, K Klingel, DY Huang, CE Müller, SC Robson, H Osswald, HK Eltzschig |
The FASEB Journal | 2007 |
CD39/NTPDase-1 activity and expression in normal leukocytes
ED Pulte, MJ Broekman, KE Olson, JH Drosopoulos, JR Kizer, N Islam, AJ Marcus |
Thrombosis Research | 2007 |
The Nucleoside Triphosphate Diphosphohydrolase-1/CD39 Is Incorporated into Human Immunodeficiency Type 1 Particles, Where It Remains Biologically Active
C Barat, G Martin, AR Beaudoin, J Sévigny, MJ Tremblay |
Journal of Molecular Biology | 2007 |
Targeted Deletion of Ectonucleoside Triphosphate Diphosphohydrolase 1/CD39 Leads to Desensitization of Pre- and Postsynaptic Purinergic P2 Receptors
U Schaefer, T Machida, MJ Broekman, AJ Marcus, R Levi |
The Journal of pharmacology and experimental therapeutics | 2007 |
Characterization of Rat NTPDase1, -2, and -3 Ectodomains Refolded from Bacterial Inclusion Bodies
M Zebisch, N Sträter |
Biochemistry | 2007 |
CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia
D Pulte, KE Olson, MJ Broekman, N Islam, HS Ballard, RR Furman, AE Olson, AJ Marcus |
Journal of Translational Medicine | 2007 |
Platelet integrins and immunoreceptors
A Kasirer-Friede, ML Kahn, SJ Shattil |
Immunological Reviews | 2007 |
Specificity of the ecto-ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases
SA Lévesque, EG Lavoie, J Lecka, F Bigonnesse, J Sévigny |
British Journal of Pharmacology | 2007 |
Characterization of Schistosoma mansoni ATPDase2 gene, a novel apyrase family member
J Levano-Garcia, RA Mortara, S Verjovski-Almeida, R DeMarco |
Biochemical and Biophysical Research Communications | 2007 |
Transient changes in the localization and activity of ecto-nucleotidases in rat hippocampus following lipopolysaccharide treatment
Á Kittel, B Sperlágh, J Pelletier, J Sévigny, TL Kirley |
International Journal of Developmental Neuroscience | 2007 |
Salutary roles of CD39 in transplantation
KM Dwyer, S Deaglio, S Crikis, W Gao, K Enjyoji, TB Strom, PJ Cowan, AJ d'Apice, SC Robson |
Transplantation Reviews | 2007 |
Cell Adhesion
A Goldstein |
Tissue Engineering | 2007 |
Constraints imposed by transmembrane domains affect enzymatic activity of membrane-associated human CD39/NTPDase1 mutants
E Musi, N Islam, JH Drosopoulos |
Archives of Biochemistry and Biophysics | 2007 |