thromboxane-a2 and carprofen

Endotoxin has previously been shown to induce platelet aggregation in equine heparinised whole blood. This study aimed to determine whether platelet-activating factor or products of cyclo-oxygenase metabolism (thromboxane A2 or prostaglandins) were important in mediating the response of platelets to endotoxin. The effects of the following drugs on endotoxin-induced aggregation were investigated: aspirin, flunixin meglumine and carprofen (non-steroidal anti-inflammatory drugs); CV-3988 and WEB2086 (platelet-activating factor receptor antagonists); quinacrine (phospholipase A2 inhibitor). The effects of quinacrine on platelet aggregation in citrated platelet-rich plasma induced by ADP and platelet-activating factor were also investigated. CV-3988 and WEB2086 caused a concentration-dependent inhibition of endotoxin-induced aggregation. The non-steroidal anti-inflammatories were without effect except flunixin meglumine which produced a small inhibition of endotoxin-induced aggregation. Quinacrine had a similar effect to the platelet-activating factor antagonists, but also non-competitively inhibited platelet aggregation in citrated platelet-rich plasma. It is concluded that platelet-activating factor is a critical mediator of endotoxin-induced platelet aggregation in the horse, but that products of cyclo-oxygenase metabolism are not of importance.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Azepines; Carbazoles; Clonixin; Endotoxins; Heparin; Horses; In Vitro Techniques; Phospholipases A; Phospholipases A2; Phospholipid Ethers; Platelet Activating Factor; Platelet Aggregation; Platelet Aggregation Inhibitors; Quinacrine; Thromboxane A2; Triazoles

Prostaglandins (PGs) have been implicated as possible modulators of the immune response and various inflammatory processes. Various cell components of the immune system are sources of PGs, and mitogen or antigen stimulation of human or murine lymphocytes leads to their enhanced release. They are also released from various human and animal tumours. Thus, as cells of the immune system are both sensitive to and sources of PGs, these factors may be important as physiological immune regulators. For example, PGs of the E series are capable of inhibiting many effector functions. They have also been shown to inhibit the development of the humoral response. Although they inhibit the proliferative response to mitogens, little is known about their effects on the development of the cell-mediated immune response to antigens. The data summarized here implicate PGs, thromboxane A2 (TXA2) and prostacyclin (PGI2) in the regulation of cellular immune responses at the inductive phase. Some of these data have been reported in abstract form.

Topics: Animals; Carbazoles; Cytotoxicity, Immunologic; Epoprostenol; Immunity, Cellular; Indomethacin; Lymphocyte Activation; Mice; Prostaglandins; Thromboxane A2; Thromboxanes