title: Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma.
abstract: 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 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 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.
authors.affiliation: 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.
authors.forename: Francesca S M
authors.initials: FS
authors.lastname: Tang
authors.affiliation: Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Gloria J
authors.initials: GJ
authors.lastname: Foxley
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, NSW 2308, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
authors.affiliation: 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 ; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9713GZ Groningen, Netherlands.
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, NSW 2308, Australia.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Baines
authors.affiliation: Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW 2006, Australia ; School of Life Sciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Oliver
mesh_terms: D000368:Aged; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D014797:Vital Capacity
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D020780:Matrix Metalloproteinase 9