Abstract
Background
Eosinophils are a characteristic inflammatory cell infiltrate in both chronic rhinosinusitis (CRS) and sinonasal polyposis (SNP). The posttranslational modifications, 3-bromo-tyrosine (Br-Tyr) and 3-chloro-tyrosine (Cl-Tyr), serve as specific molecular markers for production of brominating and chlorinating oxidants, respectively, by the eosinophil peroxidase and myeloperoxidase systems of leukocytes. The aim of this study was to identify mechanisms of oxidative protein modifications in sinonasal mucosa of CRS and SNP patients by measuring Br-Tyr, Cl-Tyr, and alternative molecular markers of distinct oxidative pathways.
Methods
Levels of Br-Tyr; Cl-Tyr; di-Tyrosine (di-Tyr), a specific oxidative cross-link; ortho-tyrosine (o-Tyr) and meta-tyrosine (m-Tyr), markers for protein modification by hydroxyl radical-like oxidants; and nitro-tyrosine (NO2-Tyr), a stable product of nitric oxide (NO)–derived oxidants, were measured in anterior ethmoid mucosa tissue from CRS and SNP patients, as well as in middle turbinate mucosa from normal volunteers, using tandem mass spectrometry.
Results
Tissue levels of Br-Tyr were significantly higher in the CRS group compared with the control group (797 μmol/mol versus 515 μmol/mol tyrosine, p < 0.015), but no differences were detected for Cl-Tyr, di-Tyr, m-Tyr, o-Tyr, and NO2-Tyr. Tissue levels of both Br-Tyr and di-Tyr were significantly higher in the SNP group compared with the control group (879 μmol/mol versus 515 μmol/mol, p < 0.005; 5090 μmol/mol versus 1700 μmol/mol, p < 0.024, respectively), but no differences were detected for Cl-Tyr, m-Tyr, o-Tyr, and NO2-Tyr.
Conclusion
Br-Tyr, a molecular footprint predominantly formed by eosinophil peroxidase–catalyzed tissue damage, may serve as an objective index of CRS and SNP disease activity.
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