title: Endocannabinoids as positive or negative factors in hematopoietic cell migration and differentiation.
abstract: The ethanolamides of arachidonic, myristic and linoleic acids reduce bone marrow cell migration, while the 2-glyceryl esters of these acids enhance migration. Thus the 2 major endocannabinoids, anandamide (arachidonoyl ethanolamide) and 2-AG (2-arachidonoyl glycerol), whose structural difference lies in the nature of the end-group alone, work in opposite directions. The endocannabinoid arachidonoyl serine, a vasodilator, also reduces migration. The effect of 2-AG is mediated, in part at least, through the cannabinoid receptors, while the effect of anandamide, as well as the rest of the compounds assayed, are not mediated through them. Almost all cannabinoids tested, including anandamide and 2-AG, lead to approximate doubling of CFU-GEMM (colony-forming unit: granulocyte, erythrocyte, macrophage, megakaryocyte) colonies. The effect of anandamide is considerably more potent than that of 2-AG. A surprising dose-response increase of erythroid cells is noted in cultures with the ester cannabinoids (in the absence of the cytokine erythropoietin), while a considerable dose-response augmentation of megakaryocytes is noted in cultures with the ethanolamide cannabinoids (in the presence of erythropoietin). This is suggestive of some cross-talk between two different regulatory systems, one governed by glycoprotein ligands and the other by endocannabinoids.
authors.affiliation: Department of Pathology, Hebrew University, Medical Faculty, Jerusalem, Israel. deborahp@ekmd.huji.ac.il
authors.forename: Deborah
authors.initials: D
authors.lastname: Patinkin
authors.forename: Garry
authors.initials: G
authors.lastname: Milman
authors.forename: Aviva
authors.initials: A
authors.lastname: Breuer
authors.forename: Ester
authors.initials: E
authors.lastname: Fride
authors.forename: Raphael
authors.initials: R
authors.lastname: Mechoulam
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D063388:Endocannabinoids; D005990:Glycerol / Q000031:analogs & derivatives / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D005990:Glycerol