Inhibition of neutrophil and eosinophil adhesion to venules of rat trachea by beta 2-adrenergic agonist formoterol.
Many inflammatory mediators trigger the adhesion of leukocytes to the vascular endothelium. We sought to determine whether the beta 2-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 beta 2-adrenergic receptors. Inflammation was induced in the airways of anesthetized pathogen-free F344 rats by injecting substance P (5 micrograms/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 micrograms/kg i.v.) 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 beta 2-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 beta 2-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.
Bowden
J J
JJ
Cardiovascular Research Institute, University of California, San Francisco 94143.
Sulakvelidze
I
I
McDonald
D M
DM
D058666:Adrenergic beta-2 Receptor Agonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D014132:Trachea / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D014699:Venules / Q000187:drug effects
D058666:Adrenergic beta-2 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D010972:Platelet Activating Factor; D011412:Propanolamines; D013373:Substance P; C026777:ICI 118551; D001920:Bradykinin; D000068759:Formoterol Fumarate