Eosinophils generate brominating oxidants in allergen-induced asthma
Weijia Wu, … , Serpil C. Erzurum, Stanley L. Hazen
Weijia Wu, … , Serpil C. Erzurum, Stanley L. Hazen
Published May 15, 2000
Citation Information: J Clin Invest. 2000;105(10):1455-1463. https://doi.org/10.1172/JCI9702.
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Article

Eosinophils generate brominating oxidants in allergen-induced asthma

Abstract

Eosinophils promote tissue injury and contribute to the pathogenesis of allergen-triggered diseases like asthma, but the chemical basis of damage to eosinophil targets is unknown. We now demonstrate that eosinophil activation in vivo results in oxidative damage of proteins through bromination of tyrosine residues, a heretofore unrecognized pathway for covalent modification of biologic targets in human tissues. Mass spectrometric studies demonstrated that 3-bromotyrosine serves as a specific “molecular fingerprint” for proteins modified through the eosinophil peroxidase-H2O2 system in the presence of plasma levels of halides. We applied a localized allergen challenge to model the effects of eosinophils and brominating oxidants in human lung injury. Endobronchial biopsy specimens from allergen-challenged lung segments of asthmatic, but not healthy control, subjects demonstrated significant enrichments in eosinophils and eosinophil peroxidase. Baseline levels of 3-bromotyrosine in bronchoalveolar lavage (BAL) proteins from mildly allergic asthmatic individuals were modestly but not statistically significantly elevated over those in control subjects. After exposure to segmental allergen challenge, lung segments of asthmatics, but not healthy control subjects, exhibited a >10-fold increase in BAL 3-bromotyrosine content, but only two- to threefold increases in 3-chlorotyrosine, a specific oxidation product formed by neutrophil- and monocyte-derived myeloperoxidase. These results identify reactive brominating species produced by eosinophils as a distinct class of oxidants formed in vivo. They also reveal eosinophil peroxidase as a potential therapeutic target for allergen-triggered inflammatory tissue injury in humans.

Authors

Weijia Wu, Michael K. Samoszuk, Suzy A.A. Comhair, Mary Jane Thomassen, Carol F. Farver, Raed A. Dweik, Mani S. Kavuru, Serpil C. Erzurum, Stanley L. Hazen

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Quantification of 3-bromotyrosine content in proteins recovered from non...
Quantification of 3-bromotyrosine content in proteins recovered from nonasthmatic and asthmatic subjects at baseline and after segmental allergen challenge. Healthy control and allergic asthmatic subjects underwent fiberoptic bronchoscopy, and a specific segment of one lung was lavaged with normal saline to obtain a baseline sample (t = 0 hours). Two specific segments in the contralateral lung were then each exposed to allergen. One of these was lavaged 10 minutes later with normal saline (10 minutes) to assess the immediate effect of allergen challenge. Forty-eight hours later, fiberoptic bronchoscopy was repeated and the other allergen-challenged lung segment was lavaged with normal saline (48 hours). Cells in the BAL were removed by centrifugation, and the content of 3-bromotyrosine on proteins recovered in the supernatant at baseline and after segmental allergen challenge was then determined by stable isotope dilution GC/MS. P values represent the comparison between t = 0 versus 48 hours for allergen-challenged lung segments in asthmatic subjects (n = six per group).