Inhibition by fenoterol of human eosinophil functions including beta2-adrenoceptor-independent actions.
Agonists at beta2 adrenoceptors are used widely as bronchodilators in treating bronchial asthma. These agents also may have important anti-inflammatory effects on eosinophils in asthma. We examined whether widely prescribed beta2-adrenoceptor agonists differ in ability to suppress stimulus-induced eosinophil effector functions such as superoxide anion (O2-) generation and degranulation. To examine involvement of cellular adhesion in such responses, we also investigated effects of beta2 agonists on cellular adhesion and on CD11b expression by human eosinophils. O2- was measured using chemiluminescence. Eosinophil degranulation and adhesion were assessed by a radioimmunoassay for eosinophil protein X (EPX). CD11b expression was measured by flow cytometry. Fenoterol inhibited platelet-activating factor (PAF)-induced O2- generation by eosinophils significantly more than salbutamol or procaterol. Fenoterol partially inhibited PAF-induced degranulation by eosinophils similarly to salbutamol or procaterol. Fenoterol inhibited phorbol myristate acetate (PMA)-induced O2- generation and degranulation by eosinophils, while salbutamol or procaterol did not. Fenoterol inhibition of PMA-induced O2- generation was not reversed by ICI-118551, a selective beta2-adrenoceptor antagonist. Fenoterol, but not salbutamol or procaterol, significantly inhibited PAF-induced eosinophil adhesion. Fenoterol inhibited O2- generation and degranulation more effectively than salbutamol or procaterol; these effects may include a component involving cellular adhesion. Inhibition also might include a component not mediated via beta2 adrenoceptors.
Tachibana
A
A
Department of Paediatrics, Gunma University School of Medicine, Gunma, Japan.
Kato
M
M
Kimura
H
H
Fujiu
T
T
Suzuki
M
M
Morikawa
A
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D039481:CD11b Antigen / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005280:Fenoterol / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D017265:Procaterol / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; D013481:Superoxides; D005280:Fenoterol; D013755:Tetradecanoylphorbol Acetate; D000420:Albuterol; D017265:Procaterol