title: Equine peritoneal macrophage production of thromboxane and prostacyclin in response to platelet activating factor and its receptor antagonist SRI 63-441.
abstract: The formation of eicosanoids may be a primary route through which platelet activating factor (PAF) exerts its effects during endotoxemia. Since endotoxemia is a common cause of death in horses, a study was conducted to determine whether PAF could stimulate equine macrophage release of thromboxane A2 (TxA2) and prostacyclin (PGI2) and whether a PAF-receptor antagonist would alter macrophage eicosanoid synthesis. Equine peritoneal macrophages were cultured from clinically normal horses and exposed to various concentrations of PAF, the PAF-receptor antagonist SRI 63-441, endotoxin, or a combination of these. The supernatant concentrations of TxB2 and 6-keto-prostaglandin F1 alpha were determined after 6 hr incubation. The media concentration of TxB2 was increased significantly above baseline after treatment of macrophages with PAF (10(-7) to 10(-5) M), and the magnitude was similar to that induced by endotoxin. This TxB2 increase was not prevented by prior treatment of macrophages with SRI 63-441. SRI 63-441 (greater than or equal to 5 x 10(-5) M) significantly enhanced macrophage TxA2 synthesis, as well as its production of PGI2, similar to the effects of endotoxin. Media concentrations of 6-keto-prostaglandin F1 alpha were not increased significantly above baseline after treatment of macrophages with PAF (10(-8) to 10(-5) M). These results suggest that PAF may cause increased TxA2 release during endotoxemia, which may not be preventable by use of the PAF-receptor antagonist SRI-63-441, which is capable of inhibiting PAF-induced aggregation of equine platelets.
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602.
authors.forename: D D
authors.initials: DD
authors.lastname: Morris
authors.forename: J N
authors.initials: JN
authors.lastname: Moore
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D004926:Escherichia coli; D005260:Female; D006736:Horses / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010529:Peritoneal Cavity / Q000166:cytology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D011806:Quinolinium Compounds / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D004731:Endotoxins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011806:Quinolinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C050531:SRI 63-441; D000001:Calcimycin; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol