Thromboxane B₂ (TxB₂) release during IgE anaphylaxis in the rabbit

Intravenous antigen challenge of specifically IgE-sensitized rabbits resulted within 30 sec in significant elevations of plasma thromboxane B₂ (TxB₂) levels. Maximal TxB₂ release (5 to 15 ng/ml) occurred within 120 to 180 sec after antigen challenge and was accompanied by the secretion of platelet factor 4 (PF4); however, PF4 release was delayed approximately 30 sec when compared to TxB₂ release. Simultaneously, basopenia, thrombocytopenia, and neutropenia occurred within 30 sec after antigen challenge with maxiaml depression by 60 sec. Intraperitoneal administration of aspirin (acetyl salicylic acid, 100 mg/kg) 18 hr before antigen challenge did not prevent the development of thrombocytopenia, neutropenia, basopenia, or the release of PF4, but significantly reduced the release of TxB₂. However, 7 of 10 aspirin-treated IgE rabbits died within 5 min after antigen challenge compared to no fatalities in 8 nonaspirin treated IgE rabbits. Since previous studies have demonstrated that platelet-activating factor (PAF) is released into the circulation during anaphylaxis, the dose-response characteristics of PAF-induced rabbit platelet secretion of serotonin and PF4 were compared to TxB₂ production in vitro. Platelet synthesis of TxB₂ was PAF dose dependent as was the secretion of serotonin and PF4; initial TxB₂ synthesis (40 pg/ml) occurred at a PAF concentration that stimulated the release of 30% serotonin and 40 ng/ml PF4. The results of these in vivo and in vitro studies suggest that TxB₂ release in the circulation during IgE-induced anaphylaxis in the rabbit may, in part, be due to PAF stimulation of thromboxane synthesis by circulating rabbit platelets; however, arachidonic acid metabolism through the cyclooxygenase pathway is not required for the alterations in circulating blood cells and platelet PF4 secretion and may, in fact, serve to attenuate the IgE anaphylactic syndrome.