title: 2-Arachidonoylglycerol enhances platelet formation from human megakaryoblasts.
abstract: Platelets modulate vascular system integrity, and their loss is critical in haematological pathologies and after chemotherapy. Therefore, identification of molecules enhancing platelet production would be useful to counteract thrombocytopenia. We have previously shown that 2-arachidonoylglycerol (2-AG) acts as a true agonist of platelets, as well as it commits erythroid precursors toward the megakaryocytic lineage. Against this background, we sought to further interrogate the role of 2-AG in megakaryocyte/platelet physiology by investigating terminal differentiation, and subsequent thrombopoiesis. To this end, we used MEG-01 cells, a human megakaryoblastic cell line able to produce in vitro platelet-like particles. 2-AG increased the number of cells showing ruffled surface and enhanced surface expression of specific megakaryocyte/platelet surface antigens, typical hallmarks of terminal megakaryocytic differentiation and platelet production. Changes in cytoskeleton modeling also occurred in differentiated megakaryocytes and blebbing platelets. 2-AG acted by binding to CB1 and CB2 receptors, because specific antagonists reverted its effect. Platelets were split off from megakaryocytes and were functional: they contained the platelet-specific surface markers CD61 and CD49, whose levels increased following stimulation with a natural agonist like collagen. Given the importance of 2-AG for driving megakaryopoiesis and thrombopoiesis, not surprisingly we found that its hydrolytic enzymes were tightly controlled by classical inducers of megakaryocyte differentiation. In conclusion 2-AG, by triggering megakaryocyte maturation and platelet release, may have clinical efficacy to counteract thrombocytopenia-related diseases.
authors.affiliation: a Department of Experimental Medicine & Surgery ; University of Rome Tor Vergata ; Rome , Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Gasperi
authors.forename: Luciana
authors.initials: L
authors.lastname: Avigliano
authors.forename: Daniela
authors.initials: D
authors.lastname: Evangelista
authors.forename: Sergio
authors.initials: S
authors.lastname: Oddi
authors.forename: Valerio
authors.initials: V
authors.lastname: Chiurchiù
authors.forename: Mirko
authors.initials: M
authors.lastname: Lanuti
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.forename: Maria
authors.initials: M
authors.lastname: Valeria Catani
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D019070:Cell Lineage; D003599:Cytoskeleton / Q000187:drug effects; D063388:Endocannabinoids / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D034061:Thrombopoiesis / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; C094503:glyceryl 2-arachidonate
keywords: 2-AG, 2-arachidonoylglycerol; AEA, anandamide; APC, allophycocyanin; CB1, type-1 cannabinoid receptor; CB2, type-2 cannabinoid receptor; CD, cluster of differentiation; DAGL, diacylglycerol lipase; Differentiation; FAAH, fatty acid amide hydrolase; FITC, fluorescein isothiocyanate; HEL, human erythroleukemia; MAGL, monoacylglycerol lipase; PE, phycoerythrin; TPA, 12-O-tetradecanoylphorbol-13-acetate; cluster of differentiation; cytoskeleton; eCB, endocannabinoid; endocannabinoid system; haematopoietic cells; megakaryocytes; platelets