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: D D Morris, J N Moore
• Journal: Circulatory shock (Circ Shock) Vol. 28 Issue 2 Pg. 149-58 (Jun 1989) ISSN: 0092-6213 [Print] United States
• PMID: 2544315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Endotoxins
• Platelet Activating Factor
• Platelet Membrane Glycoproteins
• Quinolinium Compounds
• Receptors, Cell Surface
• Receptors, G-Protein-Coupled
• platelet activating factor receptor
• SRI 63-441
• Calcimycin
• Thromboxane B2
• Thromboxane A2
• 6-Ketoprostaglandin F1 alpha
• Epoprostenol

Topics

• 6-Ketoprostaglandin F1 alpha (biosynthesis)
• Animals
• Calcimycin (pharmacology)
• Endotoxins (pharmacology)
• Epoprostenol (biosynthesis)
• Escherichia coli
• Female
• Horses (metabolism)
• Macrophages (drug effects, metabolism)
• Male
• Peritoneal Cavity (cytology)
• Platelet Activating Factor (antagonists & inhibitors, pharmacology)
• Platelet Membrane Glycoproteins
• Quinolinium Compounds (pharmacology)
• Receptors, Cell Surface (drug effects, physiology)
• Receptors, G-Protein-Coupled
• Thromboxane A2 (biosynthesis)
• Thromboxane B2 (biosynthesis)