The influence of platelet activating factor on the effects of platelet agonists and antiplatelet agents in vitro.
We assessed the effect of the intercellular mediator of inflammation, platelet activating factor (PAF), on platelet function. The interaction between PAF and the platelet agonists ADP, thrombin and convulxin was analyzed in vitro in whole blood with the use of flow cytometry and was further characterized with the use of receptor antagonists to PAF (ABT-491), P2Y1 (MRS-2179), and P2Y12 (cangrelor) as well as a monoclonal anti-PSGL-1 antibody (anti-CD162). Low concentrations of PAF (0.1 nM) synergistically augmented platelet activation induced by other agonists (P < 0.01). Augmentation by PAF was receptor mediated and did not require platelet-leukocyte interaction. With >99% inhibition of P2Y receptor-mediated platelet activation, greater than additive activation was still observed with the combination of ADP plus PAF. Accordingly, PAF synergistically augments platelet activation in response to ADP and thrombin, and the extent of inhibition exerted by P2Y receptor antagonists is decreased in the presence of PAF.
Keating
Friederike K
FK
Department of Medicine, University of Vermont-Fletcher Allen Health Care, Burlington, VT 05401, USA. friederike.keating@vtmednet.org
Schneider
David J
DJ
D000244:Adenosine Diphosphate / Q000819:agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism*; D003435:Crotalid Venoms / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000819:agonists / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000819:agonists / Q000494:pharmacology*; D010979:Platelet Function Tests; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D013917:Thrombin / Q000819:agonists / Q000494:pharmacology*
D003435:Crotalid Venoms; D037181:Lectins, C-Type; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; C028890:convulxin; D000244:Adenosine Diphosphate; D013917:Thrombin