Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma

Respiratory Research

Research

Patricia Cano¹  Jean-Pierre Lavoie¹  Amandine Vargas¹  Isabelle Bazin¹  Roxane Boivin¹  Yoana Murcia¹ 

[1] Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, 3200, rue Sicotte, J2S 2M2, Saint-Hyacinthe, Quebec, Canada;

关键词: Neutrophil activation;    Neutrophil extracellular traps and glucocorticosteroids;   

DOI  :  10.1186/s12931-017-0689-4

 received in 2017-07-11, accepted in 2017-11-27,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundSevere neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway.MethodsSix neutrophilic severe asthmatic horses and six healthy controls were studied while being treated with dexamethasone. Lung function, bronchoalveolar lavage fluid (BALF) cytology and NETs formation, as well as the expression of CD11b and CD13 by blood and airway neutrophils were evaluated. The expression of IL-17 and its role in NETs formation were also studied.ResultsAirway neutrophils from asthmatic horses, as opposed to blood neutrophils, enhanced NETs formation, which was then decreased by GC. GC also tended to decrease the expression of CD11b in blood neutrophils, but not in airway neutrophils. IL-17 mRNA was increased in BALF cells of asthmatic horses and was unaffected by GC. However, both GC and IL-17 inhibited NETs formation in vitro.ConclusionGC decreased NETs formation in vitro and also in vivo in the lungs of asthmatic horses. However, airway neutrophil activation during asthmatic inflammation was otherwise relatively insensitive to GC. The contribution of IL-17 to these responses requires further study.

【 授权许可】

CC BY   
© The Author(s). 2017