2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces the migration of EoL-1 human eosinophilic leukemia cells and human peripheral blood eosinophils.
2-arachidonoylglycerol (2-AG) is an endogenous cannabinoid receptor ligand. To date, two types of cannabinoid receptors have been identified: the CB1 receptor, abundantly expressed in the brain, and the CB2 receptor, expressed in various lymphoid tissues such as the spleen. The CB1 receptor has been assumed to play an important role in the regulation of synaptic transmission, whereas the physiological roles of the CB2 receptor remain obscure. In this study, we examined whether the CB2 receptor is present in human eosinophils and found that the CB2 receptor is expressed in human peripheral blood eosinophils. In contrast, human neutrophils do not contain a significant amount of the CB2 receptor. We then examined the effect of 2-AG on the motility of eosinophils. We found that 2-AG induces the migration of human eosinophilic leukemia EoL-1 cells. The migration evoked by 2-AG was abolished in the presence of SR144528, a CB2 receptor antagonist, or by pretreatment of the cells with pertussis toxin, suggesting that the CB2 receptor and Gi/o are involved in the 2-AG-induced migration. The migration of EoL-1 cells induced by 2-AG was suggested to be a result of chemotaxis. In contrast to 2-AG, neither anandamide nor free arachidonic acid elicited the migration. Finally, we examined the effect of 2-AG on human peripheral blood eosinophils and neutrophils and found that 2-AG induces migration of eosinophils but not neutrophils. These results suggest that the CB2 receptor and its endogenous ligand 2-AG may be closely involved in allergic inflammation accompanied by the infiltration of eosinophils.
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan.
Saori
S
Oka
Shinobu
S
Ikeda
Seishi
S
Kishimoto
Maiko
M
Gokoh
Shin
S
Yanagimoto
Keizo
K
Waku
Takayuki
T
Sugiura
D016718:Arachidonic Acid / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology*; D001892:Camphanes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D063388:Endocannabinoids; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects / Q000378:metabolism; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D017681:Hypereosinophilic Syndrome; D006967:Hypersensitivity / Q000378:metabolism* / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D037342:Pertussis Toxin / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D001095:Arachidonic Acids; D001892:Camphanes; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D016718:Arachidonic Acid; C094503:glyceryl 2-arachidonate; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C078814:anandamide