Inhibition by fenoterol of human eosinophil functions including beta2-adrenoceptor-independent actions

Clin Exp Immunol. 2002 Dec;130(3):415-23. doi: 10.1046/j.1365-2249.2002.01997.x.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / pharmacology
  • Anti-Inflammatory Agents / pharmacology*
  • CD11b Antigen / immunology
  • Cell Adhesion / drug effects
  • Cell Degranulation / drug effects
  • Cells, Cultured
  • Depression, Chemical
  • Eosinophils / drug effects*
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Fenoterol / pharmacology*
  • Flow Cytometry
  • Humans
  • Procaterol / pharmacology
  • Superoxides / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Adrenergic beta-Agonists
  • Anti-Inflammatory Agents
  • CD11b Antigen
  • Superoxides
  • Fenoterol
  • Tetradecanoylphorbol Acetate
  • Albuterol
  • Procaterol