Extensive eosinophil degranulation and peroxidase-mediated oxidation of airway proteins do not occur in a mouse ovalbumin-challenge model of pulmonary inflammation

K. L. Denzler, M. T. Borchers, J. R. Crosby, G. Cieslewicz, E. M. Hines, J. P. Justice, S. A. Cormier, K. A. Lindenberger, W. Song, W. Wu, S. L. Hazen, G. J. Gleich, J. J. Lee, N. A. Lee

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101 Scopus citations

Abstract

Paradigms of eosinophil effector function in the lungs of asthma patients invariably depend on activities mediated by cationic proteins released from secondary granules during a process collectively referred to as degranulation. In this study, we generated knockout mice deficient for eosinophil peroxidase (EPO) to assess the role(s) of this abundant secondary granule protein in an OVA-challenge model. The loss of EPO had no effect on the development of OVA-induced pathologies in the mouse. The absence of phenotypic consequences in these knockout animals extended beyond pulmonary histopathologies and airway changes, as EPO-deficient animals also displayed OVA-induced airway hyperresponsiveness after provocation with methacholine. In addition, EPO-mediated oxidative damage of proteins (e.g., bromination of tyrosine residues) recovered in bronchoalveolar lavage from OVA-treated wild-type mice was <10% of the levels observed in bronchoalveolar lavage recovered from asthma patients. These data demonstrate that EPO activities are inconsequential to the development of allergic pulmonary pathologies in the mouse and suggest that degranulation of eosinophils recruited to the lung in this model does not occur at levels comparable to those observed in humans with asthma.

Original languageEnglish (US)
Pages (from-to)1672-1682
Number of pages11
JournalJournal of Immunology
Volume167
Issue number3
DOIs
StatePublished - Aug 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Denzler, K. L., Borchers, M. T., Crosby, J. R., Cieslewicz, G., Hines, E. M., Justice, J. P., Cormier, S. A., Lindenberger, K. A., Song, W., Wu, W., Hazen, S. L., Gleich, G. J., Lee, J. J., & Lee, N. A. (2001). Extensive eosinophil degranulation and peroxidase-mediated oxidation of airway proteins do not occur in a mouse ovalbumin-challenge model of pulmonary inflammation. Journal of Immunology, 167(3), 1672-1682. https://doi.org/10.4049/jimmunol.167.3.1672