Chemotaxis of human peripheral blood eosinophils to 2-arachidonoylglycerol: Comparison with other eosinophil chemoattractants

Background: 2-Arachidonoylglycerol (2-AG), an endogenous ligand for the cannabinoid receptors (CB1 and CB2), has been shown to exhibit a variety of cannabimimetic activities in vitro and in vivo. Recently, we found that human eosinophilic leukemia EoL-1 cells and human peripheral blood eosinophils express the CB2 receptor. We also found that 2-AG induces the migration of these cells in a CB2 receptor-dependent manner. In this study, we investigated whether the 2-AG-induced migration of human eosinophils is due to chemotaxis or chemokinesis. We also compared the ability of 2-AG to induce the migration of eosinophils with those of other eosinophil chemoattractants. Methods: Eosinophils were separated from the peripheral blood of healthy donors. The migration of eosinophils to various stimulants was examined using Transwell (TM) inserts. In view of the fact that 2-AG is rapidly metabolized by cells, we employed 2-AG ether, an ether-linked nonhydrolyzable analog of 2-AG, instead of 2-AG to determine whether the 2-AG-induced migration is due to chemotaxis or chemokinesis. Results:2-AG ether induced the migration of human eosinophils, like 2-AG. The 2-AG ether-induced migration was reduced by the coincubation of eosinophils with 2-AG ether in the upper compartment of the Transwell inserts, indicating that the migration is attributable to chemotaxis. The concentration of 2-AG required to induce the eosinophil migration appears to be pathophysiologically relevant, although the order of the pharmacologically effective concentration of 2-AG was approximately ten times lower than those of platelet-activating factor, RANTES and eotaxin. Conclusion: These results strongly suggest that 2-AG is involved in the infiltration of eosinophils during allergic inflammation. Copyright (c) 2006 S. Karger AG, Basel.