Oxidative damage to proteins of bronchoalveolar lavage fluid in patients with acute respiratory distress syndrome: evidence for neutrophil-mediated hydroxylation, nitration, and chlorination.
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.
Lamb
N J
NJ
Oxygen Chemistry Laboratory, Unit of Critical Care, National Heart and Lung Institute, Imperial College of Science Technology and Medicine, London, UK.
Gutteridge
J M
JM
Baker
C
C
Evans
T W
TW
Quinlan
G J
GJ
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
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