Physiological roles of 2-arachidonoylglycerol in inflammation and immunity

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In this study, we first examined the roles of the CB2 receptor and 2-AG in allergic inflammation. We found that the level of 2-AG was dramatically augmented in the mouse ear with chronic contact dermatitis. Notably, treatment with SR144528, a CB2 receptor antagonist, markedly reduced allergic inflammation. These results strongly suggest that the CB2 receptor and its endogenous ligand 2-AG are closely involved in allergic inflammation.We then examined the effect of 2-AG on eosinophils. We found that 2-AG augmented the adhesion of human eosinophils to endothelial cells. Interestingly, treatment of the endothelial cells with SR144528 abolished thrombin- or TNF-alpha- induced adhesion of eosinophils to endothelial cells. These results suggest that the CB2 and 2-AG are also involved in the pathogenesis of the vascular system.Notably, 2-AG also induced the migration of dendritic cells. This observation suggests that 2-AG may be involved in the regulation of the immune responses.Interestingly, the cytotoxic activity of natural killer cells was markedly augmented by CB2 receptor agonists such as CP55940 and 2-AG. This finding suggests that the CB2 receptor and its endogenous ligand 2-AG are involved in the regulation of cytotoxicity of natural killer cells and play some roles in the natural immunity.We found that the phagocytic activity of macrophage-like cells was augmented following treat-ment of the cells with 2-AG, indicating that the CB2 receptor and its endogenous ligand 2-AG are also involved in the pathogenesis of inflammatory reactions in various mammalian tissues.These results strongly suggest that the CB2 receptor and its endogenous ligand 2-AG are closely involved in various types of inflammatory reactions and immune responses in mammals.