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Open Access Research article

Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma

Maria Bergquist1, Sofia Jonasson2, Josephine Hjoberg3, Göran Hedenstierna1 and Jörg Hanrieder4*

Author Affiliations

1 The Hedenstierna Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden

2 Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden

3 Respiratory & Inflammation Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden

4 Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, Gothenburg, Sweden

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BMC Pulmonary Medicine 2014, 14:110  doi:10.1186/1471-2466-14-110

Published: 4 July 2014

Abstract

Background

Improvements in asthma diagnosis and management require deeper understanding of the heterogeneity of the complex airway inflammation. We hypothesise that differences in the two major inflammatory phenotypes of asthma; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL).

Methods

BAL from mice challenged with ovalbumin (OVA/OVA) alone (standard model of asthma, here considered eosinophilic) or OVA in combination with endotoxin (OVA/LPS, model of neutrophilic asthma) was analysed using liquid chromatography coupled to high resolution mass spectrometry, and compared with steroid-treated animals and healthy controls. In addition, conventional inflammatory markers were analysed using multiplexed ELISA (Bio-Plex™ assay). Multivariate statistics was performed on integrative proteomic fingerprints using principal component analysis. Proteomic data were complemented with lung mechanics and BAL cell counts.

Results

Several of the analysed proteins displayed significant differences between the controls and either or both of the two models reflecting eosinophilic and neutrophilic asthma. Most of the proteins found with mass spectrometry analysis displayed a considerable increase in neutrophilic asthma compared with the other groups. Conversely, the larger number of the inflammatory markers analysed with Bio-Plex™ analysis were found to be increased in the eosinophilic model. In addition, major inflammation markers were correlated to peripheral airway closure, while commonly used asthma biomarkers only reflect central inflammation.

Conclusion

Our data suggest that the commercial markers we are currently relying on to diagnose asthma subtypes are not giving us comprehensive or specific enough information. The analysed protein profiles allowed to discriminate the two models and may add useful information for characterization of different asthma phenotypes.

Keywords:
Asthma; Bronchoalveolar lavage; Endotoxin; Inflammation; Ovalbumin; Proteomics; Mass spectrometry