title: 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.affiliation: Meakins-Christie Laboratories, Centre for Translational Biology, McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada. Electronic address: chantal.cossette@mcgill.ca.
authors.forename: Chantal
authors.initials: C
authors.lastname: Cossette
authors.affiliation: Meakins-Christie Laboratories, Centre for Translational Biology, McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada. Electronic address: sylvie.gravel@mcgill.ca.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gravel
authors.affiliation: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology, Melbourne, FL 32901-6982, USA. Electronic address: nchintam@fit.edu.
authors.forename: Chintam Nagendra
authors.initials: CN
authors.lastname: Reddy
authors.affiliation: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology, Melbourne, FL 32901-6982, USA. Electronic address: vivek.gore@navinta.com.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gore
authors.affiliation: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology, Melbourne, FL 32901-6982, USA. Electronic address: schourey2012@my.fit.edu.
authors.forename: Shishir
authors.initials: S
authors.lastname: Chourey
authors.affiliation: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology, Melbourne, FL 32901-6982, USA. Electronic address: qye2012@my.fit.edu.
authors.forename: Qiuji
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Center for Cancer Pharmacology, University of Pennsylvania, 854 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104-6160, USA. Electronic address: natewsnyder@gmail.com.
authors.forename: Nathaniel W
authors.initials: NW
authors.lastname: Snyder
authors.affiliation: Center for Cancer Pharmacology, University of Pennsylvania, 854 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104-6160, USA. Electronic address: mesaros@upenn.edu.
authors.forename: Clementina A
authors.initials: CA
authors.lastname: Mesaros
authors.affiliation: Center for Cancer Pharmacology, University of Pennsylvania, 854 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104-6160, USA. Electronic address: ianblair@exchange.upenn.edu.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Blair
authors.affiliation: Dept. of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, 3200 rue Sicotte, St-Hyacinthe J2S 6C7, QC, Canada. Electronic address: jean-pierre.lavoie@umontreal.ca.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lavoie
authors.affiliation: Department of Veterinary Medicine and Surgery, University of Missouri, 900 E Campus Drive, Columbia, MO 65211, USA. Electronic address: reineroc@missouri.edu.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Reinero
authors.affiliation: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology, Melbourne, FL 32901-6982, USA. Electronic address: jrokach@fit.edu.
authors.forename: Joshua
authors.initials: J
authors.lastname: Rokach
authors.affiliation: Meakins-Christie Laboratories, Centre for Translational Biology, McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada. Electronic address: william.powell@mcgill.ca.
authors.forename: William S
authors.initials: WS
authors.lastname: Powell
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000485:Allergens / Q000276:immunology; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001095:Arachidonic Acids / Q000096:biosynthesis / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D044482:Benzeneacetamides / Q000494:pharmacology; D052160:Benzothiazoles / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002415:Cats; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D031744:Cynodon / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058105:Polymerization; D061251:Primary Cell Culture; D015230:Prostaglandin D2 / Q000494:pharmacology; D018055:Receptors, Eicosanoid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D000485:Allergens; D001095:Arachidonic Acids; D044482:Benzeneacetamides; D052160:Benzothiazoles; C000589032:Gue1654; D018055:Receptors, Eicosanoid; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; D015230:Prostaglandin D2
keywords: 5-Lipoxygenase; Eicosanoids; Eosinophils; Inflammation; Neutrophils; OXE receptor