RT Journal Article
SR Electronic
T1 Modulation of neutrophil functionalities by indacaterol and their relevance for chronic lung diseases
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P851
VO 44
IS Suppl 58
A1 Bakele, Martina
A1 Winckler, Irina
A1 Hector, Andreas
A1 Hartl, Dominik
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P851.abstract
AB Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), severe asthma and cystic fibrosis (CF), are characterized by an infiltration of neutrophils into the airways. Long-acting inhaled bronchodilators (long-acting β2-agonists, LABAs) in a regularly scheduled regimen are recommended as first-line therapy in symptomatic patients with COPD. Traditionally, a potential effect of LABAs on neutrophils has been rather neglected. Recent studies, however, revealed that LABAs may represent key modulators of neutrophil effector responses by exerting a “neutrophil-stabilising” effect, but the underlying modes of actions, in particular in the context of COPD, are poorly understood. Therefore, we comprehensively studied the effect of the LABA indacaterol on homeostasis and effector functionalities of human neutrophils. These studies demonstrate that indacaterol modulates neutrophilic surface marker expression profiles, particularly downregulates CD11b/integrin surface expression, while upregulating CD62L and preventing PMA-induced CD62L shedding. These results were validated by analysing the effect of indacaterol on COPD airway fluid-induced neutrophil activation. These studies confirmed the “neutrophil dampening” effect of indacaterol. At the cellular level, indacaterol did not impair the anti-bacterial neutrophil functions, such as phagocytosis or granule release. When viewed in combination, these data support the notion that indacterol modulates neutrophilic inflammation by dampening, but not impairing, neutrophil responses, which may have implications for the neutrophilic inflammation in COPD and other chronic lung diseases.