title: Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Maria
authors.initials: M
authors.lastname: Bergquist
authors.forename: Sofia
authors.initials: S
authors.lastname: Jonasson
authors.forename: Josephine
authors.initials: J
authors.lastname: Hjoberg
authors.forename: Göran
authors.initials: G
authors.lastname: Hedenstierna
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, Gothenburg, Sweden. jorg.hanrieder@chalmers.se.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hanrieder
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D004195:Disease Models, Animal; D004804:Eosinophils; D005260:Female; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D018836:Inflammation Mediators / Q000032:analysis*; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D013058:Mass Spectrometry; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils; D010047:Ovalbumin; D010641:Phenotype; D040081:Protein Array Analysis; D020543:Proteome / Q000032:analysis* / Q000187:drug effects; D015656:Respiratory Mechanics
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D020543:Proteome; D016210:Methacholine Chloride; D010047:Ovalbumin; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone