title: Oxidative damage to proteins of bronchoalveolar lavage fluid in patients with acute respiratory distress syndrome: evidence for neutrophil-mediated hydroxylation, nitration, and chlorination.
abstract: OBJECTIVE
  To assess the degree, source, and patterns of oxidative damage to bronchoalveolar lavage proteins as a modification of amino acid residues in patients with acute respiratory distress syndrome (ARDS).
  
  
  METHODS
  Prospective, controlled study.
  
  
  METHODS
  Adult intensive care unit of a postgraduate teaching hospital.
  
  
  METHODS
  Twenty-eight patients with established ARDS were studied and compared with six ventilated patients without ARDS and 11 normal healthy controls.
  
  
  METHODS
  Supportive techniques appropriate to ARDS.
  
  
  RESULTS
  Evidence of oxidative modification of bronchoalveolar lavage fluid protein, indicative of the production of specific reactive oxidizing species, was sought using a high-performance liquid chromatography technique. Bronchoalveolar lavage fluid samples from patients with ARDS, ventilated intensive care controls, and normal healthy controls were analyzed. Concentrations of orthotyrosine were significantly higher in the ARDS group than in either control group (7.98 + 3.78 nmol/mg for ARDS, 0.67 + 0.67 for ventilated controls, and 0.71 + 0.22 for healthy controls; p < .05). Chlorotyrosine concentrations were also significantly increased in the ARDS group over either control group (4.82 + 1.07 nmol/mg for ARDS, 1.55 + 1.34 for ventilated controls, and 0.33 + 0.12 for healthy controls; p < .05). Nitrotyrosine concentrations were similarly significantly increased in the ARDS groups compared with each control group (2.21 + 0.65 nmol/mg for ARDS, 0.29 + 0.29 for ventilated controls, and 0.06 + 0.03 for healthy controls; p < .05). Chlorotyrosine and nitrotyrosine concentrations showed significant correlations with myeloperoxidase concentrations in bronchoalveolar lavage fluid, measured using an enzyme-linked immunosorbent assay in patients with ARDS. These findings suggest a possible relationship between inflammatory cell activation, oxidant formation, and damage to proteins in the lungs of these patients
  
  
  CONCLUSIONS
  Overall, our data strongly suggest heightened concentrations of oxidative stress in the lungs of patients with ARDS that lead to significantly increased oxidative protein damage.
authors.affiliation: Oxygen Chemistry Laboratory, Unit of Critical Care, National Heart and Lung Institute, Imperial College of Science Technology and Medicine, London, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Lamb
authors.forename: J M
authors.initials: JM
authors.lastname: Gutteridge
authors.forename: C
authors.initials: C
authors.lastname: Baker
authors.forename: T W
authors.initials: TW
authors.lastname: Evans
authors.forename: G J
authors.initials: GJ
authors.lastname: Quinlan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D006900:Hydroxylation; D006997:Hypochlorous Acid / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000276:immunology*; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D018709:Statistics, Nonparametric; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D015415:Biomarkers; D009566:Nitrates; D016877:Oxidants; D011506:Proteins; C039642:peroxynitric acid; D017665:Hydroxyl Radical; C002744:3-nitrotyrosine; D014443:Tyrosine; C026741:2-tyrosine; D006997:Hypochlorous Acid; C087259:3-chlorotyrosine