Characterization of oxidative pathways in chronic rhinosinusitis and sinonasal polyposis.

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 micromol/mol versus 515 micromol/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 micromol/mol versus 515 micromol/mol, p < 0.005; 5090 micromol/mol versus 1700 micromol/mol, p < 0.024, respectively), but no differences were detected for Cl-Tyr, m-Tyr, o-Tyr, and NO2-Tyr.

CONCLUSIONS

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.