title: Systemic upregulation of neutrophil α-defensins and serine proteases in neutrophilic asthma.
abstract: BACKGROUND
  The well-characterised airway inflammatory phenotypes of asthma include eosinophilic, neutrophilic, mixed eosinophilic/neutrophilic and paucigranulocytic asthma, identified based on the proportion of sputum granulocytes. Systemic inflammation is now recognised as an important part of some airway diseases, but the involvement of systemic inflammation in the pathogenesis of airway inflammatory phenotypes of asthma remains unknown.
  
  
  METHODS
  Induced sputum samples and peripheral blood were collected from participants with asthma (n=36). Airway inflammatory cell counts were performed from induced sputum and inflammatory phenotype assigned based on the airway eosinophil and neutrophil cut-offs of 3% and 61%, respectively. RNA was extracted from whole blood and gene expression profiles were generated (Illumina Humanref-8 V3) and analysed using GeneSpring GX11.
  
  
  RESULTS
  There were six genes classified as differentially expressed between the four asthma phenotypes, including the α-defensins (DEFA) 1, 1B, 3 and 4 and neutrophil proteases cathepsin G (CTSG) and elastase (ELA2). Systemic expression of DEFA1,1B,3,4,CTSG and ELA2 was significantly higher in the neutrophilic asthma (NA) phenotype. Microarray results of the α-defensins and neutrophil proteases were successfully validated using real-time PCR. Plasma elastase was significantly increased in people with neutrophilic airway inflammation.
  
  
  CONCLUSIONS
  There is systemic upregulation of α-defensin and neutrophil protease expression in NA, which may represent proinflammatory effects on the bone marrow and the release of immature neutrophils into the circulation. This demonstrates a systemic inflammatory component in NA that further differentiates this from other asthma phenotypes and indicates different mechanisms in NA.
authors.affiliation: Priority Research Centre forAsthma and Respiratory Diseases, The University of Newcastle, Callaghan, Australia. katherine.baines@newcastle.edu.au
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Baines
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Simpson
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Wood
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
mesh_terms: D000368:Aged; D001249:Asthma / Q000097:blood*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D057057:Serine Proteases / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D013183:Sputum / Q000166:cytology; D015854:Up-Regulation; D023084:alpha-Defensins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
chemical_list: D023084:alpha-Defensins; D057057:Serine Proteases