IMPORTANCE OF PLATELETS IN THE PROCESS LEADING TO PAI-1 INCREASE FOLLOWING ENDOTOXEMIA IN-VIVO

Endotoxin producing bacteria cause disseminated intravascular coagulation, The mechanism of endotoxin action is still unclear but impairment of the fibrinolytic system has been suggested as a contributing mechanism. A single injection of endotoxin (1 mu g/kg, i.v.) dramatically increased the circulating activity of plasma PAI-1 in the rabbit, This effect occurred in time-dependent manner, the maximum activity of circulating PAI-1 being observed 4 h after the administration of endotoxin. In order to determine the importance of platelets in this phenomenon, we administered and-platelet antiserum which reduced platelet counts to 6% of the basal value, Antiserum-induced thrombocytopenia did not alter the effect of endotoxin showing that PAI-1 increase resulting from the injection of endotoxin did not depend on platelet release directly or indirectly. This observation was further confirmed by the effect of various antithrombotic agents, known for their effects on platelets, tested for their ability to affect endotoxin-induced PAI-1 increase. Indeed, neither antiplatelet agents like clopidogrel, an ADP antagonist, SR 27417, a selective PAF receptor antagonist, SR 46349, a 5-HT2 receptor antagonist, L-NAME a nitric oxide synthase inhibitor or aspirin nor anticoagulants like heparin of hirudin, administered intravenously before the administration of endotoxin showed any activity with regard to PAI-1 increase, Therefore, we show that PAI-1 increase resulting from the injection of endotoxin do not depend on platelet release directly or indirectly.