Role of phosphoinositide 3-kinase in adhesion of platelets to fibrinogen stimulated by cancer procoagulant

Abstract

Cancer procoagulant, cysteine proteinase (CP; EC 3.4.22.26) activates factor X and functions in the absence of factor VII. CP may also change the platelet function. It induces an increase of platelet adhesion to collagen and fibrinogen. Using wortmannin - the inhibitor of phosphoinositide 3-kinase (PI 3-K) we studied the role of this enzyme in the action of cancer procoagulant on blood platelet adhesion in vitro . Wortmannin (25, 50 and 100 nM, 30 min, 37°C) caused a reduction of platelet adhesion to fibrinogen ( P <0.01) when blood platelets were stimulated by both 0.2 U/ml thrombin (IC 50 ~75 nM) and by 1 w M ADP (IC 50 ~60 nM). We observed that after CP treatment the adhesion of thrombin-activated and ADP-stimulated platelets to fibrinogen was augmented. The potentiated by CP adhesion of activated platelets to fibrinogen was reduced after preincubation of platelets with wortmannin (50 nM, 30 min, 37°C). We conclude that in adhesion of platelets to fibrinogen stimulated by CP PI 3-K take place.