Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners
Anne-Sophie Archambault,
Julyanne Brassard,
Émilie Bernatchez,
Cyril Martin,
Vincenzo Di Marzo,
Michel Laviolette,
Louis-Philippe Boulet,
Marie-Renée Blanchet,
Nicolas Flamand
Affiliations
Anne-Sophie Archambault
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médecine, Faculté de Médecine, Université Laval, Quebec City, QC G1V 4G5, Canada
Julyanne Brassard
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médecine, Faculté de Médecine, Université Laval, Quebec City, QC G1V 4G5, Canada
Émilie Bernatchez
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médecine, Faculté de Médecine, Université Laval, Quebec City, QC G1V 4G5, Canada
Cyril Martin
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médecine, Faculté de Médecine, Université Laval, Quebec City, QC G1V 4G5, Canada
Vincenzo Di Marzo
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médecine, Faculté de Médecine, Université Laval, Quebec City, QC G1V 4G5, Canada
Michel Laviolette
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médecine, Faculté de Médecine, Université Laval, Quebec City, QC G1V 4G5, Canada
Louis-Philippe Boulet
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médecine, Faculté de Médecine, Université Laval, Quebec City, QC G1V 4G5, Canada
Marie-Renée Blanchet
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médecine, Faculté de Médecine, Université Laval, Quebec City, QC G1V 4G5, Canada
Nicolas Flamand
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médecine, Faculté de Médecine, Université Laval, Quebec City, QC G1V 4G5, Canada
High eosinophil (EOS) counts are a key feature of eosinophilic asthma. EOS notably affect asthmatic response by generating several lipid mediators. Mice have been utilized in hopes of defining new pharmacological targets to treat asthma. However, many pinpointed targets in mice did not translate into clinics, underscoring that key differences exist between the two species. In this study, we compared the ability of human (h) and mouse (m) EOS to biosynthesize key bioactive lipids derived from arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). hEOS were isolated from the blood of healthy subjects and mild asthmatics, while mEOSs were differentiated from the bone marrow. EOSs were treated with fatty acids and lipid mediator biosynthesis assessed by LC-MS/MS. We found that hEOS biosynthesized leukotriene (LT) C4 and LTB4 in a 5:1 ratio while mEOS almost exclusively biosynthesized LTB4. The biosynthesis of the 15-lipoxygenase (LO) metabolites 15-HETE and 12-HETE also differed, with a 15-HETE:12-HETE ratio of 6.3 for hEOS and 0.727 for mEOS. EOS biosynthesized some specialized pro-resolving mediators, and the levels from mEOS were 9-times higher than those of hEOS. In contrast, hEOS produced important amounts of the endocannabinoid 2-arachidonoyl-glycerol (2-AG) and its congeners from EPA and DHA, a biosynthetic pathway that was up to ~100-fold less prominent in mEOS. Our data show that hEOS and mEOS biosynthesize the same lipid mediators but in different amounts. Compared to asthmatics, mouse models likely have an amplified involvement of LTB4 and specialized pro-resolving mediators and a diminished impact of the endocannabinoid 2-arachidonoyl-glycerol and its congeners.
