Effects Of Beta 2-Adrenergic Agonists On House Dust Mite-Induced Adhesion, Superoxide Anion Generation, And Degranulation Of Human Eosinophils

Background: Even in subjects who are not sensitized to house dust mite (HDM), allergic symptoms can be clinically aggravated by exposure to dust. We previously reported that Dermatophagoides farinae (Df), an important HDM, or Der f 1, a major allergen of Df, induced the effector functions of eosinophils, which may be an important mechanism for HDM-induced symptoms in nonsensitized patients. In a clinical setting, beta(2)-adrenergic agonists, such as salbutamol and formoterol, are used for the treatment of asthma attacks or exacerbation to release the airway obstruction. Several reports have suggested that some beta(2)-adrenergic agonists have an anti-inflammatory capacity.Objective: In this study, we investigated whether beta(2)-adrenergic agonist could modify the Df-or Der f 1-induced activation of eosinophils.Methods: Blood eosinophils obtained from healthy donors were preincubated with either formoterol (1 mu M), salbutamol (1 mu M), or buffer control and then stimulated with Df extract (1 mu g/mL) or Der f 1 (100 pg/mL). Eosinophil adhesion to intercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. Generation of superoxide anion (O-2(-)) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by enzyme-linked immunosorbent assay.Results: Formoterol, but not salbutamol, suppressed the Df- or Der f 1-induced eosinophil adhesion to ICAM-1. Furthermore, formoterol, but not salbutamol, suppressed Df- induced O-2(-) generation or EDN release. Neither formoterol nor salbutamol suppressed spontaneous eosinophil adhesion, O-2(-) generation, or EDN release.Conclusion: These findings suggested that formoterol, but not salbutamol, suppressed Df- or Der f1-induced eosinophil activation when used at the same concentration. Therefore, formoterol could potentially be used for the treatment of bronchial asthma via both bronchodilation and anti-inflammatory effect.