Nature Medicine
5, 1010 - 1017 (1999)
doi:10.1038/12447
Targeted disruption of cd39/ATP diphosphohydrolase results in
disordered hemostasis and thromboregulationKeiichi Enjyoji1, Jean Sévigny2, Yuan Lin2, Paul S. Frenette3, Patricia D. Christie1, Jan Schulte Am Esch II2, Masato Imai2, Jay M. Edelberg1, Helen Rayburn1, Miroslaw Lech1, David L. Beeler1, Eva Csizmadia2, Denisa D. Wagner3, Simon C. Robson2, 4
& Robert D. Rosenberg1, 41
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
2
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
3
Department of Pathology, Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
4
SCR & RDR are joint senior authors
Correspondence should be addressed to Robert D. Rosenberg rdrrosen@mit.eduCD39, or vascular adenosine triphosphate diphosphohydrolase, has been considered
an important inhibitor of platelet activation. Unexpectedly, cd39-deficient
mice had prolonged bleeding times with minimally perturbed coagulation parameters.
Platelet interactions with injured mesenteric vasculature were considerably
reduced in vivo and purified mutant platelets failed to aggregate to
standard agonists in vitro. This platelet hypofunction was reversible
and associated with purinergic type P2Y1 receptor desensitization. In keeping
with deficient vascular protective mechanisms, fibrin deposition was found
at multiple organ sites in cd39-deficient mice and in transplanted
cardiac grafts. Our data indicate a dual role for adenosine triphosphate diphosphohydrolase
in modulating hemostasis and thrombotic reactions.
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