Effect of beta2-adrenergic agonists on eosinophil adhesion, superoxide anion generation, and degranulation.
BACKGROUND
Eosinophils play important roles in the development of asthma exacerbation. Viral infection is a major cause of asthma exacerbation, and the expression of IFN-γ-inducible protein of 10 kDa (IP-10) and cysteinyl leukotrienes (cysLTs) is up-regulated in virus-induced asthma. As β2-adrenergic agonists, such as formoterol or salbutamol, are used to treat asthma exacerbation, we examined whether formoterol or salbutamol could modify eosinophil functions such as adhesiveness, particularly those activated by cysLTs or IP-10.


METHODS
Eosinophils were isolated from the blood of healthy subjects and were pre-incubated with either formoterol or salbutamol, and subsequently stimulated with IL-5, LTD4, or IP-10. Adhesion of eosinophils to intercellular cell adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. The generation of eosinophil superoxide anion (O2(-)) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) release was evaluated by ELISA as a marker of degranulation.


RESULTS
Neither formoterol nor salbutamol suppressed the spontaneous adhesion of eosinophils to ICAM-1. However, when eosinophils were activated by IL-5, LTD4, or IP-10, formoterol, but not salbutamol, suppressed the adhesion to ICAM-1. Formoterol also suppressed IL-5, LTD4, or IP-10 induced eosinophil O2(-) generation or EDN release.


CONCLUSIONS
These findings suggest that formoterol, but not salbutamol, suppresses eosinophil functions enhanced by IL-5, LTD4, or IP-10. As these factors are involved in the development of asthma exacerbation, our results strongly support the hypothesis that administration of formoterol is a novel strategy for treating asthma exacerbation.
Allergy Center, Saitama Medical University, Saitama, Japan; Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan; Department of General Internal Medicine, Saitama Medical University, Saitama, Japan.
Toru
T
Noguchi
Allergy Center, Saitama Medical University, Saitama, Japan; Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan. Electronic address: nakagomek-tky@umin.ac.jp.
Kazuyuki
K
Nakagome
Allergy Center, Saitama Medical University, Saitama, Japan; Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan; Department of General Internal Medicine, Saitama Medical University, Saitama, Japan.
Takehito
T
Kobayashi
Allergy Center, Saitama Medical University, Saitama, Japan; Department of Pediatrics, Saitama Medical University, Saitama, Japan.
Yutaka
Y
Ueda
Allergy Center, Saitama Medical University, Saitama, Japan; Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
Tomoyuki
T
Soma
Department of General Internal Medicine, Saitama Medical University, Saitama, Japan.
Hidetomo
H
Nakamoto
Allergy Center, Saitama Medical University, Saitama, Japan; Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
Makoto
M
Nagata
D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects* / Q000276:immunology*; D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D000068759:Formoterol Fumarate / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015848:Interleukin-5 / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D055815:Young Adult
D058666:Adrenergic beta-2 Receptor Agonists; D054357:Chemokine CXCL10; D015848:Interleukin-5; D018343:Receptors, Adrenergic, beta-2; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D017998:Leukotriene D4; D000420:Albuterol; D000068759:Formoterol Fumarate
Adhesion molecule; Beta2-adrenergic agonist; Chemokine; Cysteinyl leukotrienes; Eosinophils