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

Abstract:

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. CONCLUSION:These results strongly suggest that 2-AG is involved in the infiltration of eosinophils during allergic inflammation.

authors

Kishimoto S,Oka S,Gokoh M,Sugiura T

doi

10.1159/000092704

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

3-7

eissn

1018-2438

issn

1423-0097

pii

92704

journal_volume

140 Suppl 1

pub_type

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