title: Study of the role of cytosolic phospholipase A2 alpha in eicosanoid generation and thymocyte maturation in the thymus.
abstract: The thymus is a primary lymphoid organ, home of maturation and selection of thymocytes for generation of functional T-cells. Multiple factors are involved throughout the different stages of the maturation process to tightly regulate T-cell production. The metabolism of arachidonic acid by cyclooxygenases, lipoxygenases and specific isomerases generates eicosanoids, lipid mediators capable of triggering cellular responses. In this study, we determined the profile of expression of the eicosanoids present in the mouse thymus at different stages of thymocyte development. As the group IVA cytosolic phospholipase A2 (cPLA2α) catalyzes the hydrolysis of phospholipids, thereby generating arachidonic acid, we further verified its contribution by including cPLA2α deficient mice to our investigations. We found that a vast array of eicosanoids is expressed in the thymus, which expression is substantially modulated through thymocyte development. The cPLA2α was dispensable in the generation of most eicosanoids in the thymus and consistently, the ablation of the cPLA2α gene in mouse thymus and the culture of thymuses from human newborns in presence of the cPLA2α inhibitor pyrrophenone did not impact thymocyte maturation. This study provides information on the eicosanoid repertoire present during thymocyte development and suggests that thymocyte maturation can occur independently of cPLA2α.
authors.affiliation: Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, Québec, QC, Canada.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rousseau
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA, the United States of America.
authors.forename: Gajendra S
authors.initials: GS
authors.lastname: Naika
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, Québec, QC, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Perron
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, Québec, QC, Canada.
authors.forename: Frederic
authors.initials: F
authors.lastname: Jacques
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA, the United States of America.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.affiliation: Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, Québec, QC, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Boilard
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002675:Child, Preschool; D003600:Cytosol / Q000201:enzymology*; D015777:Eicosanoids / Q000096:biosynthesis* / Q000145:classification; D018507:Gene Expression Regulation, Developmental; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D015398:Signal Transduction; D060168:Thymocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D046509:Tissue Culture Techniques
chemical_list: D015777:Eicosanoids; D064801:Phospholipase A2 Inhibitors; D011759:Pyrrolidines; C455981:pyrrophenone; D054513:Group IV Phospholipases A2