Involvement of Adenosine A2 Receptors in the Changes of Tissue Factor-Dependent Coagulant Activity Induced by Polymorphonuclear Leukocytes in Endothelial Cells

We have already reported that polymorphonuclear leukocytes (PMNs) could increase tissue factor-dependent coagulant activity (TF activity) in endothelial cells mediated by adhesion of PMNs to endothelial cells. In the present study, the role of adenosine receptors in the changes of TF activity and of adhesion between PMNs and endothelial cells was examined. The increases of the TF activity and adhesion were significantly reduced in a concentration-dependent manner by pretreatment of adenosine (0.1 and 1.0 mM); an adenosine A1/A2-receptor agonist, CGS-21680 (5, 10 and 50 microM); and an adenosine A2-receptor agonist, 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 1.0, 10 and 100 nM). An adenosine A2-receptor antagonist, 3,7-dimethyl-1-(2-propynyl) xanthine (DMPX; 1.0 and 100 nM), antagonized significantly the reduction of the TF activity and the adhesion induced by adenosine (1.0 mM), while 8-cyclopentyl-1,3-dimethylxanthine (CPDMX; 1.0 and 100 nM), an adenosine A1-receptor antagonist, did not affect it. On the other hand, the TF activity and the adhesion were not changed by N6-cyclohexyladenosine (CHA; 10 and 100 nM) and 2-chloro-N-cyclopentyladenosine (CCPA; 10 and 100 nM), adenosine A1-receptor agonists in the same conditions. These results suggest that the reduction in the TF activity stimulated by PMNs is closely related to the adhesive inhibition between PMNs and endothelial cells through the adenosine A2-receptor-mediated system.