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].