Biosynthesis and actions of 5-oxoeicosatetraenoic acid (5-oxo-ETE) on feline granulocytes.

Abstract

The 5-lipoxygenase product 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is the most powerful human eosinophil chemoattractant among lipid mediators and could play a major pathophysiological role in eosinophilic diseases such as asthma. Its actions are mediated by the OXE receptor, orthologs of which are found in many species from humans to fish, but not rodents. The unavailability of rodent models to examine the pathophysiological roles of 5-oxo-ETE and the OXE receptor has substantially hampered progress in this area. As an alternative, we have explored the possibility that the cat could serve as an appropriate animal model to investigate the role of 5-oxo-ETE. We found that feline peripheral blood leukocytes synthesize 5-oxo-ETE and that physiologically relevant levels of 5-oxo-ETE are present in bronchoalveolar lavage fluid from cats with experimentally induced asthma. 5-Oxo-ETE (EC50, 0.7nM) is a much more potent activator of actin polymerization in feline eosinophils than various other eicosanoids, including leukotriene (LT) B4 and prostaglandin D2. 5-Oxo-ETE and LTB4 induce feline leukocyte migration to similar extents at low concentrations (1nM), but at higher concentrations the response to 5-oxo-ETE is much greater. Although high concentrations of selective human OXE receptor antagonists blocked 5-oxo-ETE-induced actin polymerization in feline granulocytes, their potencies were about 200 times lower than for human granulocytes. We conclude that feline leukocytes synthesize and respond to 5-oxo-ETE, which could potentially play an important role in feline asthma, a common condition in this species. The cat could serve as a useful animal model to investigate the pathophysiological role of 5-oxo-ETE.

• Authors: Chantal Cossette, Sylvie Gravel, Chintam Nagendra Reddy, Vivek Gore, Shishir Chourey, Qiuji Ye, Nathaniel W Snyder, Clementina A Mesaros, Ian A Blair, Jean-Pierre Lavoie, Carol R Reinero, Joshua Rokach, William S Powell
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 96 Issue 3 Pg. 247-55 (Aug 01 2015) ISSN: 1873-2968 [Electronic] England
• PMID: 26032638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Actins
• Allergens
• Arachidonic Acids
• Benzeneacetamides
• Benzothiazoles
• Gue1654
• Receptors, Eicosanoid
• 5-oxo-6,8,11,14-eicosatetraenoic acid
• Leukotriene B4
• Arachidonate 5-Lipoxygenase
• Prostaglandin D2

Topics

• Actins (genetics, metabolism)
• Allergens (immunology)
• Animals
• Arachidonate 5-Lipoxygenase (genetics, metabolism)
• Arachidonic Acids (biosynthesis, pharmacology)
• Asthma (chemically induced, genetics, immunology, metabolism)
• Benzeneacetamides (pharmacology)
• Benzothiazoles (pharmacology)
• Bronchoalveolar Lavage Fluid (cytology)
• Cats
• Chemotaxis (drug effects, immunology)
• Cynodon (chemistry, immunology)
• Disease Models, Animal
• Eosinophils (drug effects, metabolism, pathology)
• Female
• Gene Expression
• Humans
• Leukotriene B4 (pharmacology)
• Male
• Neutrophils (drug effects, metabolism, pathology)
• Polymerization
• Primary Cell Culture
• Prostaglandin D2 (pharmacology)
• Receptors, Eicosanoid (antagonists & inhibitors, genetics, metabolism)