Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma

BMC Pulmonary Medicine

Jörg Hanrieder³  Göran Hedenstierna⁴  Josephine Hjoberg¹  Sofia Jonasson²  Maria Bergquist⁴ 

[1] Respiratory & Inflammation Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden;Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden;Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, Gothenburg, Sweden;The Hedenstierna Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden

关键词: Mass spectrometry;    Proteomics;    Ovalbumin;    Inflammation;    Endotoxin;    Bronchoalveolar lavage;    Asthma;   

Others  :  1109597
DOI  :  10.1186/1471-2466-14-110

 received in 2014-01-20, accepted in 2014-06-12,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Bergquist et al.; licensee BioMed Central Ltd.

【 图 表 】

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