| Title | Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma. | ||
| Author | Tang, Francesca S M; Foxley, Gloria J; Gibson, Peter G; Burgess, Janette K; Baines, Katherine J; Oliver, Brian G | ||
| Journal | Mediators Inflamm | Publication Year/Month | 2015 |
| PMID | 26663987 | PMCID | PMC4667029 |
| Affiliation + expend | 1.Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW 2006, Australia ; Discipline of Pharmacology, School of Medical Sciences, Faculty of Medicine, The University of Sydney, Sydney, NSW 2006, Australia. | ||
BACKGROUND: Respiratory infections are a major cause of asthma exacerbations where neutrophilic inflammation dominates and is associated with steroid refractory asthma. Structural airway cells in asthma differ from nonasthmatics; however it is unknown if neutrophils differ. We investigated neutrophil immune responses in patients who have good (AGood) and suboptimal (ASubopt) asthma symptom control. METHODS: Peripheral blood neutrophils from AGood (ACQ < 0.75, n = 11), ASubopt (ACQ > 0.75, n = 7), and healthy controls (HC) (n = 9) were stimulated with bacterial (LPS (1 mug/mL), fMLF (100 nM)), and viral (imiquimod (3 mug/mL), R848 (1.5 mug/mL), and poly I:C (10 mug/mL)) surrogates or live rhinovirus (RV) 16 (MOI1). Cell-free supernatant was collected after 1 h for neutrophil elastase (NE) and matrix metalloproteinase- (MMP-) 9 measurements or after 24 h for CXCL8 release. Results. Constitutive NE was enhanced in AGood neutrophils compared to HC. fMLF stimulated neutrophils from ASubopt but not AGood produced 50% of HC levels. fMLF induced MMP-9 was impaired in ASubopt and AGood compared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1 and FEV1/FVC. ASubopt and AGood responded similarly to other stimuli. CONCLUSIONS: Circulating neutrophils are different in asthma; however, this is likely to be related to airflow limitation rather than asthma control.