Acetyl glyceryl ether phosphorylcholine (AGEPC) is a mediator of inflammation and anaphylaxis, released from IgE-sensitized basophils when exposed to antigens. Convincing evidence shows that AGEPC is synthesized by inflammatory cells, and its mechanism of action has been extensively studied with particular interest focusing on platelet stimulation, the key event initiating the inflammatory cascade. However, widely different results have been reported so that the mode of action of AGEPC in activating platelets is still largely obscure. The objective of this investigation was to elucidate whether AGEPC stimulates human platelets independently from arachidonate metabolism, as previously suggested, and to define the role of nonsteroidal antiinflammatory drugs in inhibiting AGEPC-mediated platelet activation. Irreversible platelet agggregation in vitro occurred at low AGEPC concentrations, was dose dependent, and was accompanied by thromboxane A2 formation. Aspirin inhibited irreversible aggregation induced by low AGEPC concentrations. A thromboxane inhibitor, UK-37,248-01, failed to affect AGEPC aggregation, suggesting a crucial role for cyclic endoperoxides in AGEPC's mechanism of action. A thromboxane/endoperoxide receptor antagonist 13-azaprostanoic acid prevented irreversible platelet aggregation induced by low AGEPC concentrations. The inhibiting effect of aspirin on AGEPC aggregation could be overcome by increasing the concentration of the agonist by a factor of 10, unless a lipoxygenase inhibitor, nordihydroguaiaretic acid, or 5,8,11,14-eicosatetraynoic acid was previously added to platelet-rich plasmas. The phospholipase inhibitor, mepacrine, completely suppressed human platelet aggregation induced by AGEPC. These results indicate that AGEPC induces irreversible aggregation in human platlets by two distinct pathways, both dependent upon arachidonic acid metabolism: a cyclooxygenase-dependent one at low AGEPC concentrations and a cyclooxygenase-independent one, possibly mediated through the formation of lipoxygenase products, at high AGEPC concentrations.
|Number of pages||10|
|Publication status||Published - 1985|
ASJC Scopus subject areas
- Pathology and Forensic Medicine