CD39 and platelets
Platelets are known to express both CD39 and CD73 on their surface[104]. CD39 rapidly and preferentially metabolizes
ATP and ADP released from activated platelets into AMP, thereby
drastically reducing or even abolishing platelet aggregation and
recruitment [105]. Unlike P2Y12R inhibitors and
GPIIb/IIIa blockers, CD39 does not directly interfere with platelets;
instead, it clears ADP around the platelets and maintains platelet
functions [106]. A recombinant soluble form of
human CD39 strongly inhibits human platelet aggregation induced by
agonists [107-109]. Mice over-expressing human
CD39 are resistant to arterial thrombosis induced by oxidative damage,
which may be due to the decreased activation of platelet fibrinogen
receptor αIIb/β3 [110]. CD39-null mice manifest an
increase in circulating platelet-leukocyte heteroaggregates, which
suggests the presence of heterotypic crosstalk between the coagulation
process and inflammatory systems [111]. The
expression of CD39 and CD73 increases significantly on the platelet
surface upon stimulation with thrombin, which indicates a
thrombin-mediated externalization of these ectonucleotidases[112]. Although CD39 has been considered an
important inhibitor of platelet activation, Enjyoji et al. reported that
CD39 knockout paradoxically leads to disordered hemostasis, and they
speculate there is a dual role for adenosine triphosphate
diphosphohydrolase in modulating hemostasis and thrombotic
reactions.[113].