2-Arachidonoylglycerol enhances platelet formation from human megakaryoblasts

Valeria Gasperi, Luciana Avigliano, Daniela Evangelista, Sergio Oddi, Valerio Chiurchiuà, Mirko Lanuti, Mauro Maccarrone, Maria Valeria Catani

Research output: Contribution to journalArticlepeer-review

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-speci fic 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.

Original languageEnglish
Pages (from-to)3938-3947
Number of pages10
JournalCell Cycle
Volume13
Issue number24
DOIs
Publication statusPublished - Dec 15 2014

Keywords

  • Cluster of differentiation
  • Cytoskeleton
  • Differentiation
  • Endocannabinoid system
  • Haematopoietic cells
  • Megakaryocytes
  • Platelets

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology
  • Medicine(all)

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