Salbutamol delays human eosinophil apoptosis via a cAMP-dependent mechanism - 02/08/11
![](/templates/common/images/mail.png)
![](/templates/common/images/mail.png)
![](/templates/common/images/mail.png)
![](/templates/common/images/mail.png)
![](/templates/common/images/mail.png)
![](/templates/common/images/entites/lowast.gif)
Abstract |
Eosinophils play a major role in asthma. One described mechanism leading to the impaired clearance of these cells from the lung is the delay in their programmed cell death (apoptosis). β2-Adrenoceptor agonists have been shown to prolong survival and delay apoptosis of eosinophils. The aim of the present study was to evaluate the mechanisms, especially the role of cAMP pathway, in the prolongation of human eosinophil survival by a selective β2-agonist salbutamol.
Isolated human peripheral blood eosinophils were cultured in the absence or presence of a β2-agonist salbutamol and the indicated antagonists/inhibitors under sterile conditions. Apoptosis was measured by using the relative DNA fragmentation assay and Annexin-V binding.
Salbutamol prolonged survival of human eosinophils and it was inhibited by a β-receptor antagonist propranolol and mimicked by cell-permeant cAMP analogues dibutyryl- and 8-bromo-cAMP. Pharmacological inhibitors of adenylyl cyclase (SQ-22,536) and protein kinase A (Rp-8-CPT-cAMPS) antagonized the effects of salbutamol. The survival-prolonging action of salbutamol was potentiated by a phosphodiesterase inhibitor rolipram (EC50 for the salbutamol effect was 13.6±4.0 and 8.1±3.1nM in the absence and presence of rolipram, respectively; p=0.0142, n=10). In contrast, inhibition of Ca2+-activated K+-channels by apamin, charybdotoxin, iberiotoxin or paxilline did not affect the ability of salbutamol to prolong eosinophil survival.
Taken together, the present results suggest that salbutamol at clinically relevant concentrations decreases apoptosis in human eosinophils by activating the cannonical β2-receptor-adenylyl cyclase–cAMP-protein kinase A pathway.
Le texte complet de cet article est disponible en PDF.Keywords : Eosinophils, Apoptosis, Salbutamol, cAMP
Abbreviations : Apamin, cAMP, Charybdotoxin, COPD, Iberiotoxin, NS-1619, paxilline, PDE, PI, PI3K, PKA, Rp-8-CPT-cAMPS, SQ-22,536
Plan
Vol 24 - N° 4
P. 394-400 - août 2011 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?