title: 2-arachidonoylglycerol induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes through the cannabinoid CB2 receptor-dependent mechanism.
abstract: 2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors (CB1 and CB2) and has been shown to exhibit a variety of cannabimimetic activities in vitro and in vivo. Recently, we proposed that 2-arachidonoylglycerol is the true endogenous ligand for the cannabinoid receptors, and both receptors (CB1 and CB2) are primarily 2-arachidonoylglycerol receptors. The CB1 receptor is assumed to be involved in the attenuation of neurotransmission. On the other hand, the physiological roles of the CB2 receptor, which is abundantly expressed in several types of leukocytes such as macrophages, still remain unknown. In this study, we examined the effects of 2-arachidonoylglycerol on the motility of HL-60 cells differentiated into macrophage-like cells. We found that 2-arachidonoylglycerol induces the migration of differentiated HL-60 cells. The migration induced by 2-arachidonoylglycerol was blocked by treatment of the cells with either SR144528, a CB2 receptor antagonist, or pertussis toxin, suggesting that the CB2 receptor and Gi/Go are involved in the 2-arachidonoylglycerol-induced migration. Several intracellular signaling molecules such as Rho kinase and mitogen-activated protein kinases were also suggested to be involved. In contrast to 2-arachidonoylglycerol, anandamide, another endogenous cannabinoid receptor ligand, failed to induce the migration. The 2-arachidonoylglycerol-induced migration was also observed for two other types of macrophage-like cells, the U937 cells and THP-1 cells, as well as human peripheral blood monocytes. These results strongly suggest that 2-arachidonoylglycerol induces the migration of several types of leukocytes such as macrophages/monocytes through a CB2 receptor-dependent mechanism thereby stimulating inflammatory reactions and immune responses.
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan.
authors.forename: Seishi
authors.initials: S
authors.lastname: Kishimoto
authors.forename: Maiko
authors.initials: M
authors.lastname: Gokoh
authors.forename: Saori
authors.initials: S
authors.lastname: Oka
authors.forename: Mayumi
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kajiwara
authors.forename: Keizo
authors.initials: K
authors.lastname: Waku
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sugiura
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001095:Arachidonic Acids; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology*; D063388:Endocannabinoids; D005989:Glycerides / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D008264:Macrophages / Q000502:physiology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D018377:Neurotransmitter Agents; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C094503:glyceryl 2-arachidonate