Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners
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 int...
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MDPI AG
2022-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/1/141 |
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| author | Anne-Sophie Archambault Julyanne Brassard Émilie Bernatchez Cyril Martin Vincenzo Di Marzo Michel Laviolette Louis-Philippe Boulet Marie-Renée Blanchet Nicolas Flamand |
| author_facet | Anne-Sophie Archambault Julyanne Brassard Émilie Bernatchez Cyril Martin Vincenzo Di Marzo Michel Laviolette Louis-Philippe Boulet Marie-Renée Blanchet Nicolas Flamand |
| author_sort | Anne-Sophie Archambault |
| collection | DOAJ |
| description | 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) C<sub>4</sub> and LTB<sub>4</sub> in a 5:1 ratio while mEOS almost exclusively biosynthesized LTB<sub>4</sub>. 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 LTB<sub>4</sub> and specialized pro-resolving mediators and a diminished impact of the endocannabinoid 2-arachidonoyl-glycerol and its congeners. |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:45:28Z |
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| spelling | doaj.art-856dc54cb86245238bfddc77045af8582023-11-23T11:20:48ZengMDPI AGCells2073-44092022-01-0111114110.3390/cells11010141Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its CongenersAnne-Sophie Archambault0Julyanne Brassard1Émilie Bernatchez2Cyril Martin3Vincenzo Di Marzo4Michel Laviolette5Louis-Philippe Boulet6Marie-Renée Blanchet7Nicolas Flamand8Centre 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, CanadaCentre 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, CanadaCentre 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, CanadaCentre 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, CanadaCentre 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, CanadaCentre 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, CanadaCentre 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, CanadaCentre 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, CanadaCentre 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, CanadaHigh 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) C<sub>4</sub> and LTB<sub>4</sub> in a 5:1 ratio while mEOS almost exclusively biosynthesized LTB<sub>4</sub>. 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 LTB<sub>4</sub> and specialized pro-resolving mediators and a diminished impact of the endocannabinoid 2-arachidonoyl-glycerol and its congeners.https://www.mdpi.com/2073-4409/11/1/141eosinophileicosanoiddocosanoidleukotrieneprostaglandinsspecialized pro-resolving mediators |
| spellingShingle | Anne-Sophie Archambault Julyanne Brassard Émilie Bernatchez Cyril Martin Vincenzo Di Marzo Michel Laviolette Louis-Philippe Boulet Marie-Renée Blanchet Nicolas Flamand Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners Cells eosinophil eicosanoid docosanoid leukotriene prostaglandins specialized pro-resolving mediators |
| title | Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners |
| title_full | Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners |
| title_fullStr | Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners |
| title_full_unstemmed | Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners |
| title_short | Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners |
| title_sort | human and mouse eosinophils differ in their ability to biosynthesize eicosanoids docosanoids the endocannabinoid 2 arachidonoyl glycerol and its congeners |
| topic | eosinophil eicosanoid docosanoid leukotriene prostaglandins specialized pro-resolving mediators |
| url | https://www.mdpi.com/2073-4409/11/1/141 |
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