IMPORTANCE OF PLATELET-ACTIVATING-FACTOR IN ANAPHYLAXIS-INDUCED T-PA AND PAI-1 INCREASE IN THE RABBIT

Single injections of ovalbumin to presensitized rabbits dramatically i ncreased the circulating activities of plasma tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) and induc ed a severe thrombocytopenia. These effects occurred in a time- and do se-dependent manner, the maximum circulating levels of t-PA and PAI-1 being observed 30 min after administration of the antigen. In order to determine the importance of platelet activating factor (PAF) in this phenomenon, SR 27417, a potent and selective PAF receptor antagonist, was administered prior to antigen challenge, The intravenous administr ation of SR 27417 strongly inhibited the effects of ovalbumin, showing that t-PA and PAI-1 increase resulting from the anaphylaxis reaction depend on PAF release. SR 27417 also strongly inhibited ovalbumin-indu ced thrombocytopenia. The mechanism of action of PAF leading to t-PA a nd PAI-1 increase during anaphylaxis is still unclear, but might be co nsidered as a contributing mechanism during the allergic reaction.