Effect of emedastine difumarate on CC chemokine-elicited eosinophil migration

Emedastine difumarate (emedastine) is an antiallergic drug found among the derivatives which has a series of benzimidazole frames. It has been reporte d that emedastine can significantly inhibit the migration of eosinophils el icited by classical chemoattractants, including LTB4 or PAF. However, the e ffect of emedastine on the selective migration of eosinophils that have bee n stimulated with CC chemokines has not been examined. Emedastine at concen trations of 10 nM or higher strongly inhibited the eosinophil migration eli cited by CC chemokines, including eotaxin, RANTES and MCP-3. Preincubation of the eosinophils with emedastine did not alter the expression of the CCR3 receptor, although a decrease in the concentration of intracellular calciu m ions was observed after stimulation with 100 ng/ml of eotaxin. Herbimycin A, genistein, staurosporin and emedastine were all able to inhibit the eot axin-elicited migration. Tyrosine kinase activity in the cytosol supernatan t of eosinophils obtained after stimulation with eotaxin significantly decr eased when the eosinophils were preincubated with emedastine. In addition, protein kinase A and protein kinase C activities in eotaxin-stimulated EoL- 1 cell supernatants decreased significantly with emedastine pretreatment. T hese findings suggest that emedastine inhibits CC chemokine-elicited eosino phil mig ration by decreasing the activities of tyrosine kinase or protein kinases but does not: alter CCR3 expression. Copyright (C) 2001 S. Karger A G, Basel.