Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma

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 (A(Good)) and suboptimal (A(Subopt)) asthma symptom control. Methods. Peripheral blood neutrophils from A(Good) (ACQ < 0.75, n = 11), A(Subopt) (ACQ > 0.75, n = 7), and healthy controls (HC) (n = 9) were stimulated with bacterial (LPS (1 μg/mL), fMLF (100 nM)), and viral (imiquimod (3 μg/mL), R848 (1.5 μg/mL), and poly I:C (10 μg/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 A(Good) neutrophils compared to HC. fMLF stimulated neutrophils from A(Subopt) but not A(Good) produced 50% of HC levels. fMLF induced MMP-9 was impaired in A(Subopt) and A(Good) compared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV(1) and FEV(1)/FVC. A(Subopt) and A(Good) 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.