Platelets Release a New Mediator, Platelet-Activating Factor, Which Accounts for ADP and Thromboxane-Independent Aggregation

Platelet aggregation induced by low concentrations of ionophore A23187(I) or thrombin (T) is due to ADP and to metabolites of arachidonic acid(AA) as shown by its inhibition by aspirin and by ADP scavangers. High concentrations of I or T surmount inhibition, thus involving other mediator(s) Platelet-activating factor (PAF)is a 1-lysophospholipid released from macrophages among other cells, in the presence of I. We now show that PAF is released from rabbit platelets during aggregation by I, T and collagen but not by AA nor by PAF itself. Formation and release of PAF by platelets is unaffected by cyclo-oxygenase blockers or by ADP scavengers, but is suppressed by inhibitors of phospholipase A2 activity (dibutyrylcyclic AMP and bromophenacylbromide). Platelet PAF exhibits similar absorption characteristics on silicic acid thin layer and hight pressure chromatography, and sensitivity to N. naja phospholipase A2 as compared to PAF from leukocytes. PAF may be like ADP and thromboxane A2, a Final effector for platelet aggregation and be responsible for the aspirin-resistant third pathway of platelet aggregation.