MECHANISMS OF THE PLATELET-AGGREGATION INDUCED BY ACTIVATED NEUTROPHILS AND INHIBITORY EFFECT OF SPECIFIC PAF RECEPTOR ANTAGONISTS

The supernatant of polymorphonuclear neutrophils after their activatio n by opsonized zymosan induces the aggregation of washed platelets in human. It potentiates platelet aggregation induced by agonists in plat elet rich plasma as well as in whole blood. This activation involves t he phosphoinositide metabolism. Specific PAF receptor antagonists ging kolides (BN 50726, BN 52021, BN 54068, BN 54062, BN 50730, BN 50749, B N 50744) and benzodiazepine Web2086 antagonize this neutrophil-induced platelet aggregation. BN 50 730, BN 50 749 and Web 2086 can fully inh ibit this aggregation at the final concentration of 10(-6) M. Preincub ation of platelets with synthetic PAF also inhibits this activation th rough a desensitization of the receptor. These data suggest the major involvement in our model of PAF acether in the platelet-neutrophil int eractions.