Expression of the endocannabinoid system in the bi-potential HEL cell line: Commitment to the megakaryoblastic lineage by 2-arachidonoylglycerol

Maria Valeria Catani, Filomena Fezza, Samantha Baldassarri, Valeria Gasperi, Alessandra Bertoni, Nicoletta Pasquariello, Alessandro Finazzi-Agrò, Fabiola Sinigaglia, Luciana Avigliano, Mauro Maccarrone

Research output: Contribution to journalArticlepeer-review

Abstract

The role of the endocannabinoid system in haematopoietic cells is not completely understood. We investigated whether human erythroleukemia (HEL) cells were able to bind, metabolise and transport the main endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). We also investigated whether AEA or 2-AG could modulate HEL differentiation. Although able to internalise both endocannabinoids, HEL cells had the machinery to metabolise 2-AG only, since they were devoid of the enzymes needed to synthesise and degrade AEA. Nonetheless, the intracellular transport of exogenous AEA might be required to activate the vanilloid receptors, with yet unknown implications for vascular biology. On the contrary, 2-AG appeared to play a role in lineage determination. Indeed, 2-AG itself drove HEL cells towards megakaryocytic differentiation, as it enhanced expression of β3 integrin subunit, a megakaryocyte/platelet surface antigen, and glycoprotein VI, a late marker of megakaryocytes; in parallel, it reduced the amount of messenger RNA encoding for glycophorin A, a marker of erythroid phenotype. All these effects were mediated by activation of CB2 cannabinoid receptors that triggered an extracellular signal-regulated kinase-dependent signalling cascade. In addition, classical inducers of megakaryocyte differentiation reduced 2-AG synthesis (although they did not affect the binding efficiency of CB2 receptors), suggesting that levels of this endocannabinoid may be critical for committing HEL cells towards the megakaryocytic lineage.

Original languageEnglish
Pages (from-to)65-74
Number of pages10
JournalJournal of Molecular Medicine
Volume87
Issue number1
DOIs
Publication statusPublished - Jan 2009

Keywords

  • Differentiation
  • Endocannabinoid system
  • Hematopoietic cells
  • Receptor
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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