Systemic upregulation of neutrophil α-defensins and serine proteases in neutrophilic asthma
- 1Priority Research Centre for Asthma and Respiratory Diseases, The University of Newcastle, Callaghan, Australia
- 2Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, New Lambton, Australia
- 3Priority Research Centre of Information Based Medicine, Hunter Medical Research Institute, The University of Newcastle, Callaghan, Australia
- Correspondence to Dr Katherine J Baines, Level 3, HMRI, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, Newcastle, NSW 2310, Australia;
- Received 5 January 2011
- Accepted 16 June 2011
- Published Online First 23 July 2011
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.
Conclusion 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.
- Asthma phenotypes
- systemic inflammation
- gene expression
- asthma mechanisms
- innate immunity
- neutrophil biology
Funding The University of Newcastle funded the project and KJ Baines is funded through the Hunter Medical Research Institute XStrata Coal Asthma Research Fellowship.
Competing interests None.
Ethics approval The Hunter Area Health Service ethics committee and the University of Newcastle research ethics committee approved this study.
Provenance and peer review Not commissioned; externally peer reviewed.