Differential effects of salbutamol and montelukast on eosinophil adhesion and superoxide anion generation.
BACKGROUND
Beta2-agonists, a representative class of bronchodilators used for asthma, have been shown to modulate some functions of eosinophils, including cell adhesion. Similarly, a leukotriene receptor antagonist (LTRA) may be beneficial in controlling inflammation in asthma, as cysteinyl leukotrienes (cysLTs) can cause accumulation or activation of eosinophils. Recent evidence suggests that the addition of an LTRA, but not a long-acting beta2-agonist, to inhaled corticosteroid additionally reduces the number of eosinophils in sputum and blood from patients with asthma. The present study examined whether a beta2-agonist and an LTRA differentially modify eosinophil adhesion and activation induced by cysLTs and other activators.


METHODS
Eosinophils were isolated from blood of healthy donors and then incubated in the presence or absence of salbutamol (albuterol) or montelukast. Eosinophils were then exposed to leukotriene D4 (LTD4) or another activator, and the generation of superoxide anion (O2-) was evaluated by cytochrome C reduction assay. Eosinophil adhesion was examined by an eosinophil peroxidase assay.


RESULTS
Montelukast, but not salbutamol (both at 1 microM), inhibited LTD4-induced (100 nM) eosinophil adhesion to recombinant human intercellular adhesion molecule 1. Both drugs similarly and partially inhibited the 100 pM interleukin-5-induced adhesive response of eosinophils to recombinant human intercellular adhesion molecule 1. Montelukast, but not salbutamol, blocked LTD4-induced eosinophil O2- generation of eosinophils. Finally, neither salbutamol nor montelukast modified phorbol myristate acetate (1 ng/ml)-induced O2- generation from eosinophils.


CONCLUSIONS
These results confirm that LTD4 directly induces activation of eosinophils via the cysLT1 receptor. Furthermore, the results suggest that a beta2-agonist has no effect on eosinophil adhesion and activation induced by cysLTs. These results explain the differential effects of an LTRA and a beta2-agonist in the treatment of eosinophilic inflammation in asthma.
Kushiya
Mariko
M
Department of Respiratory Medicine, Saitama Medical School, Saitama, Japan.
Saito
Keiko
K
Kikuchi
Izumi
I
Kobayashi
Takehito
T
Hagiwara
Koichi
K
Kanazawa
Minoru
M
Nagata
Makoto
M
D000085:Acetates / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003521:Cyclopropanes; D004804:Eosinophils / Q000187:drug effects*; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D013440:Sulfides; D013481:Superoxides / Q000032:analysis
D000085:Acetates; D000318:Adrenergic beta-Agonists; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D013481:Superoxides; C093875:montelukast; D000420:Albuterol