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 reported that emedastine can significantly inhibit the migration of eosinophils elicited by classical chemoattractants, including LTB4 or PAF. However, the effect of emedastine on the selective migration of eosinophils that have been stimulated with CC chemokines has not been examined. Emedastine at concentrations of 10 nM or higher strongly inhibited the eosinophil migration elicited 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 calcium ions was observed after stimulation with 100 ng/ml of eotaxin. Herbimycin A, genistein, staurosporin and emedastine were all able to inhibit the eotaxin-elicited migration. Tyrosine kinase activity in the cytosol supernatant of eosinophils obtained after stimulation with eotaxin significantly decreased 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. These findings suggest that emedastine inhibits CC chemokine-elicited eosinophil migration by decreasing the activities of tyrosine kinase or protein kinases but does not alter CCR3 expression.
Saito
H
H
Clinical Research Center for Rheumatology and Allergy, National Sagamihara Hospital, Sagamihara, Japan.
Yamamoto
N
N
Tomita
S
S
Taniguchi
M
M
Hasegawa
M
M
Akiyama
K
K
Kawaguchi
H
H
Takahashi
K
K
D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000494:pharmacology; D054410:Chemokine CCL7; D019742:Chemokines, CC / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D018945:Monocyte Chemoattractant Proteins / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
D018926:Anti-Allergic Agents; D001562:Benzimidazoles; C515456:CCL11 protein, human; C515450:CCL7 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D019742:Chemokines, CC; D016207:Cytokines; D004791:Enzyme Inhibitors; D018945:Monocyte Chemoattractant Proteins; D047428:Protein Kinase Inhibitors; C043345:emedastine; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium