Mechanisms of the platelet aggregation induced by activated neutrophils and inhibitory effect of specific PAF receptor antagonists.
The supernatant of polymorphonuclear neutrophils after their activation by opsonized zymosan induces the aggregation of washed platelets in human. It potentiates platelet aggregation induced by agonists in platelet rich plasma as well as in whole blood. This activation involves the phosphoinositide metabolism. Specific PAF receptor antagonists gingkolides (BN 50726, BN 52021, BN 54068, BN 54062, BN 50730, BN 50749, BN 50744) and benzodiazepine Web2086 antagonize this neutrophil-induced platelet aggregation. BN 50,730, BN 50,749 and Web 2086 can fully inhibit this aggregation at the final concentration of 10(-6) M. Preincubation of platelets with synthetic PAF also inhibits this activation through a desensitization of the receptor. These data suggest the major involvement in our model of PAF acether in the platelet-neutrophil interactions.
Nguyên
P
P
Laboratoire central d'Hématologie, CHU Robert-Debré, Reims, France.
Petitfrère
E
E
Potron
G
G
D017077:Culture Media, Conditioned; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015054:Zymosan / Q000494:pharmacology
D017077:Culture Media, Conditioned; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D015054:Zymosan; D000242:Cyclic AMP