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

[摘要] 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 fromAGood(ACQ < 0.75,n=11),ASubopt(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 inAGoodneutrophils compared to HC. fMLF stimulated neutrophils fromASuboptbut notAGoodproduced 50% of HC levels. fMLF induced MMP-9 was impaired inASuboptandAGoodcompared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1and FEV1/FVC.ASuboptandAGoodresponded 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.

[学科分类] 生理学与病理学