Expression of the endocannabinoid system in the bi-potential HEL cell line: commitment to the megakaryoblastic lineage by 2-arachidonoylglycerol.
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 beta3 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 CB(2) 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 CB(2) receptors), suggesting that levels of this endocannabinoid may be critical for committing HEL cells towards the megakaryocytic lineage.
Catani
Maria Valeria
MV
Department of Experimental Medicine & Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy.
Fezza
Filomena
F
Baldassarri
Samantha
S
Gasperi
Valeria
V
Bertoni
Alessandra
A
Pasquariello
Nicoletta
N
Finazzi-Agrò
Alessandro
A
Sinigaglia
Fabiola
F
Avigliano
Luciana
L
Maccarrone
Mauro
M
D000943:Antigens, Differentiation / Q000096:biosynthesis; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D063388:Endocannabinoids; D005786:Gene Expression Regulation / Q000187:drug effects*; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000378:metabolism
D000943:Antigens, Differentiation; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; C078814:anandamide