title: Inhibition of eosinophil activation in bronchoalveolar lavage fluid from atopic asthmatics by Y-24180, an antagonist to platelet-activating factor.
abstract: We examined the effects of Y-24180, a potent and long-acting antagonist to platelet-activating factor (PAF) receptor, on the expression of adhesion molecules in peripheral blood and bronchoalveolar lavage fluid (BALF) eosinophils from atopic asthmatics. Y-24180 (20 mg/day) was administered to 4 atopic asthmatics for 8 weeks. The number of eosinophils, the level of eosinophil cationic protein (ECP), the bindings of soluble intercellular adhesion molecule-1 (sICAM-1) and fibronectin (FN), and the expressions of CD11b (alpha chain of Mac-1) and CD49d (alpha chain of VLA-4) on eosinophils were evaluated in peripheral blood (n=4) and BALF (n=3) before and after the administration of Y-24180. The infiltration of eosinophils into the bronchial wall was also examined by taking biopsies. Eosinophil count, sICAM-1 and FN binding to eosinophils in BALF significantly decreased after the administration of Y-24180 (p<0.05). The level of CD11b expression also decreased remarkably after the administration (n=2). In peripheral blood, eosinophil count and ECP level did not change. The binding of sICAM-1 and FN, and expression of CD11b on eosinophils in peripheral blood showed a tendency to decrease after the administration. The level of CD49d expression on eosinophils changed neither in BALF nor in blood. Eosinophil infiltration into the bronchial wall markedly decreased in one out of 3 cases after the administration. These results suggest that Y-24180 inhibits the activation of eosinophils by antagonizing the actions of PAF in atopic asthmatics.
authors.affiliation: Health Care Center, Oita Medical University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mizuki
authors.forename: H
authors.initials: H
authors.lastname: Komatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: S
authors.initials: S
authors.lastname: Iwane
authors.forename: T
authors.initials: T
authors.lastname: Tsuda
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D001381:Azepines / Q000627:therapeutic use*; D001798:Blood Proteins / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039423:Integrin alpha1; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D012260:Ribonucleases; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D015703:Antigens, CD; D001381:Azepines; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D005353:Fibronectins; D039423:Integrin alpha1; D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D014230:Triazoles; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine; D018799:Intercellular Adhesion Molecule-1; D012260:Ribonucleases