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 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.


CONCLUSIONS
These results strongly suggest that 2-AG is involved in the infiltration of eosinophils during allergic inflammation.
Kishimoto
Seishi
S
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Oka
Saori
S
Gokoh
Maiko
M
Sugiura
Takayuki
T
D001095:Arachidonic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC / Q000494:pharmacology; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D063388:Endocannabinoids; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D010972:Platelet Activating Factor / Q000494:pharmacology; D043885:Receptor, Cannabinoid, CB2 / Q000276:immunology / Q000378:metabolism
D001095:Arachidonic Acids; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D063388:Endocannabinoids; D005989:Glycerides; D010972:Platelet Activating Factor; D043885:Receptor, Cannabinoid, CB2; C094503:glyceryl 2-arachidonate