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Increased Levels of Hypoxia-sensitive Proteins in Allergic Airway Inflammation

Department of Molecular Biosciences, Swedish University of Agricultural Sciences, The Biomedical Centre, Uppsala; Department of Medical Countermeasures, Swedish Defence Research Agency; and Department of Respiratory Medicine and Allergy, University Hospital, Umeå, Sweden

Correspondence and requests for reprints should be addressed to Professor Gunnar Pejler, Swedish University of Agricultural Sciences, Department of Molecular Biosciences, The Biomedical Centre, Box 575, 751 23 Uppsala, Sweden. E-mail: gunnar.pejler{at}vmk.slu.se

In this study we investigated the alterations in protein levels that are induced by allergic eosinophilic lung inflammation. Lung tissue eosinophilia and sequestration of inflammatory cells in airspaces were provoked by systemic sensitization with ovalbumin followed by repeated inhalation challenge with aerosolized ovalbumin. Proteome alterations in lung tissue and bronchoalveolar lavage fluid, respectively, were examined by two-dimensional gel electrophoresis followed by identification of proteins by mass spectrometry. Several proteins were markedly increased in inflamed tissue. In particular, several proteins that are known to be associated with hypoxia were elevated, for example, glycolytic enzymes, glucose-regulated protein 78 kD, prolyl-4-hydroxylase, peroxiredoxin 1, and arginase. Out of the identified proteins, Ym2 displayed the clearest increase, present at high levels in animals with lung eosinophilia, while being undetectable in control subjects. Furthermore, the levels of cathepsin S were markedly increased in inflamed tissue. Taken together, this study identifies a number of marker proteins associated with the pathogenesis of allergic lung inflammation and indicates a link between allergic airway inflammation and induction of hypoxia-related gene products.

Key Words: asthma • proteomics • hypoxia • allergy

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