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

Cancer procoagulant, cysteine proteinase (CP; EC 3.4.22.26) activates facto r X and functions in the absence of factor VII. CP may also change the plat elet 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 procoagula nt on blood platelet adhesion in vitro. Wortmannin (25, 50 and 100 nM, 30 m in, 37 degreesC) caused a reduction of platelet adhesion to fibrinogen (P<0 .01) when blood platelets were stimulated by both 0.2 U/ml thrombin (IC50<s imilar to>75 nM) and by 1 mu MADP (IC(50)similar to 60 nM). We observed tha t after CP treatment the adhesion of thrombin-activated and ADP-stimulated platelets to fibrinogen was augmented. The potentiated by CP adhesion of ac tivated platelets to fibrinogen was reduced after preincubation of platelet s with wortmannin (50 nM, 30 min, 37 degreesC). We conclude that in adhesio n of platelets to fibrinogen stimulated by CP PI 3-K take place.