Endogenous cannabinoid receptor ligand induces the migration of human natural killer cells.
2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors (CB1 and CB2). Evidence is gradually accumulating which shows that 2-arachidonoylglycerol plays important physiological roles in several mammalian tissues and cells, yet the details remain ambiguous. In this study, we first examined the effects of 2-arachidonoylglycerol on the motility of human natural killer cells. We found that 2-arachidonoylglycerol induces the migration of KHYG-1 cells (a natural killer leukemia cell line) and human peripheral blood natural killer cells. The migration of natural killer cells induced by 2-arachidonoylglycerol was abolished by treating the cells with SR144528, a CB2 receptor antagonist, suggesting that the CB2 receptor is involved in the 2-arachidonoylglycerol-induced migration. In contrast to 2-arachidonoylglycerol, anandamide, another endogenous cannabinoid receptor ligand, did not induce the migration. Delta9-tetrahydrocannabinol, a major psychoactive constituent of marijuana, also failed to induce the migration; instead, the addition of delta9-tetrahydrocannabinol together with 2-arachidonoylglycerol abolished the migration induced by 2-arachidonoylglycerol. It is conceivable that the endogenous ligand for the cannabinoid receptor, that is, 2-arachidonoylglycerol, affects natural killer cell functions such as migration, thereby contributing to the host-defense mechanism against infectious viruses and tumor cells.
Kishimoto
Seishi
S
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195.
Muramatsu
Mayumi
M
Gokoh
Maiko
M
Oka
Saori
S
Waku
Keizo
K
Sugiura
Takayuki
T
D001095:Arachidonic Acids / Q000494:pharmacology / Q000502:physiology*; D001892:Camphanes / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D063388:Endocannabinoids; D005989:Glycerides / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008024:Ligands; D011720:Pyrazoles / Q000494:pharmacology; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D001095:Arachidonic Acids; D001892:Camphanes; D063388:Endocannabinoids; D005989:Glycerides; D008024:Ligands; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; C094503:glyceryl 2-arachidonate