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Methodology for Sputum Induction and Laboratory Processing
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3-Chlorotyrosine in sputum of COPD patients: relationship with airway inflammation

Charles O'Donnell1, Paul Newbold, Peter White

  • 1DMPK, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, United Kingdom. CharlesJO'Donnell@astrazeneca.com

COPD
|December 21, 2010
PubMed

Insights

We measured 3-chlorotyrosine (3Cl-Tyr) in COPD patient sputum for the first time. Sputum 3Cl-Tyr levels strongly correlated with myeloperoxidase (MPO) activity, indicating MPO

Area of Science:

  • Pulmonary Medicine
  • Biochemistry
  • Inflammation Research

Background:

  • Airways in Chronic Obstructive Pulmonary Disease (COPD) exhibit elevated inflammatory cells, primarily neutrophils and macrophages.
  • Myeloperoxidase (MPO), a neutrophil granule enzyme, serves as a biomarker for neutrophilic inflammation in COPD and other inflammatory conditions.
  • MPO uniquely generates hypochlorous acid (HOCl), which chlorinates tyrosine residues in proteins, forming 3-chlorotyrosine (3Cl-Tyr).

Purpose of the Study:

  • To establish the presence and levels of 3-chlorotyrosine (3Cl-Tyr) in the sputum of stable COPD patients.
  • To investigate the correlation between sputum 3Cl-Tyr levels and myeloperoxidase (MPO) activity in COPD patients.

Main Methods:

  • Sputum samples were collected from 14 stable COPD patients.
  • Sol phase samples were prepared via ultra-centrifugation.
  • 3Cl-Tyr levels were quantified using Liquid Chromatography-Mass Spectrometry (LC-MSMS).
  • MPO activity was assessed using a standard chromogenic substrate assay.
  • Spearman rank correlation analysis was employed.

Main Results:

  • This study reports the first measurement of 3Cl-Tyr in sputum from stable COPD patients.
  • A strong positive correlation was observed between sputum 3Cl-Tyr levels and sputum MPO activity (r = 0.88; p < 0.0001).

Conclusions:

  • The detection of 3Cl-Tyr in COPD sputum signifies an active MPO-related process.
  • This MPO-driven activity may contribute to the underlying pathophysiology of COPD.

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