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Journal of Biochemistry 2005 137(2):217-223; doi:10.1093/jb/mvi021
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© 2005 The Japanese Biochemical Society

BIOCHEMISTRY

Endogenous Cannabinoid Receptor Ligand Induces the Migration of Human Natural Killer Cells

Seishi Kishimoto, Mayumi Muramatsu, Maiko Gokoh, Saori Oka, Keizo Waku and Takayuki Sugiura1

Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195

1 To whom correspondence should be addressed. Fax: +81-426-85-1345, E-mail: sugiurat{at}pharm.teikyo-u.ac.jp

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. {Delta}9-Tetrahydrocannabinol, a major psychoactive constituent of marijuana, also failed to induce the migration; instead, the addition of {Delta}9-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.


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