Activation of rabbit platelets by platelet-activating factor derived from IgE-sensitized basophils. Characteristics of the aggregation and its dissociation from secretion

Abstract

Platelet-activating factor (PAF) is liberated from antigen-stimulated, IgE-sensitized rabbit basophils and induces aggregation of platelets and secretion of their content of vasoactive amines. Experiments were performed to determine the relationship between these two platelet responses to this stimulus.(a) Aggregation was initiated by appreciably lower concentrations of PAF than were required to produce even minimal release of constituents. PAF-induced aggregation was also resistant to agents which destroy ADP, such as creatine phosphate/creatine phosphokinase or apyrase, and occurred with platelets made unresponsive (refractory) to ADP. It was concluded that PAF can induce aggregation by a mechanism which is distinguishable from the release reaction and from the aggregating effect of ADP.(b) Secretion can probably occur independently of aggregation because incubation without agitation resulted in secretion without detectable aggregation.(c) Despite the suggestion that the two platelet responses can be independent, they may be induced by the same stimulus. This was indicated by experiments in which platelets specifically desensitized to PAF-induced secretion were also found to be unresponsive to PAF-stimulated aggregation. Moreover, identical levels of inhibition and identical inhibition profiles were obtained for both responses with serine esterase inhibitor, diisopropylphosphofluoridate, and with amino acid esters. It was concluded that the same stimulus-specific activable protease (esterase) was most likely involved in PAF-induced aggregation and secretion.