Inhibition of neutrophil and eosinophil adhesion to venules of rat trachea by β₂-adrenergic agonist formoterol

Many inflammatory mediators trigger the adhesion of leukocytes to the vascular endothelium. We sought to determine whether the β₂-adrenergic receptor agonist formoterol can inhibit the adhesion of neutrophils and eosinophils to the endothelium of venules in the rat airway mucosa. We also tested whether this action is mediated by β₂-adrenergic receptors. Inflammation was induced in the airways of anesthetized pathogen-free F344 rats by injecting substance P (5 μg/kg) or bradykinin (10 mg/kg) intravenously. The rats were perfused with fixative 5 min later, and the tracheas were removed. Adherent intravascular neutrophils and eosinophils, stained by a histochemical reaction for myeloperoxidase, were counted in tracheal whole mounts. We found that, after the injection of substance P, formoterol (0.1, 1.0, or 10.0 μg/kg iv) reduced the number of adherent neutrophils by 8, 59, or 56% and reduced the number of eosinophils by 59, 90, or 86%, respectively. The three doses of formoterol reduced the amount of substance P-induced extravasation of Monastral blue by 21, 66, or 80%, respectively. Both effects of formoterol were blocked by the β₂-adrenergic receptor antagonist ICI-118,551, which by itself produced neither leukocyte adhesion nor plasma extravasation. After the injection of bradykinin, the three doses of formoterol reduced the number of adherent neutrophils by 28, 67, or 62% and reduced the number of eosinophils by 17, 38, or 57%, respectively. We conclude that formoterol, acting via β₂-adrenergic receptors, not only can reduce the amount of plasma leakage but also can reduce the number of neutrophils and eosinophils that adhere to the vascular endothelium at sites of inflammation.