Introduction: Ticagrelor is a dual
inhibitor of platelet P2Y12 receptors and cellular adenosine reuptake. In the
PLATO study, ticagrelor was associated with fewer pulmonary infections in ACS
patients compared to clopidogrel. We studied whether adenosine reuptake
inhibition by ticagrelor and another adenosine reuptake inhibitor,
dipyridamole, might influence leukocyte function.
Methods: Neutrophils and erythrocytes were
isolated from healthy volunteers using Histopaque ficoll gradient
centrifugation. Concentration-dependent effects of adenosine on neutrophil
chemotaxis were investigated and the involved adenosine receptors were
identified using adenosine receptor antagonists. The effects of cangrelor
(another P2Y12 inhibitor), ticagrelor and dipyridamole on IL-8-stimulated
neutrophil chemotaxis were determined over 30 minutes in the presence or
absence of i) erythrocytes and/or ii) adenosine.
Results: Low-concentration adenosine (10
nM) caused a significant increase in neutrophil chemotaxis (28.7±4.4vs.
22.6±2.4; P<0.01) in response to IL-8 through the low-affinity A1
receptor, whereas the high-affinity receptor A2a could reverse this action in
the presence of higher-concentration adenosine 10 μM (22.8±3.6 vs. 31.5±8.0;
P<0.05). Erythrocytes attenuated the effects of adenosine on neutrophil
chemotaxis in the presence of cangrelor or control whereas ticagrelor and
dipyridamole both preserved this effect of adenosine in the presence of
Conclusion: Inhibition of
adenosine reuptake by ticagrelor and dipyridamole leads to potentiation of
the effects of adenosine on neutrophil chemotaxis in the presence of
erythrocytes. This represents a potential mechanism by which ticagrelor could
influence host defence against bacterial lung infection.