title: 3-Chlorotyrosine as a marker of protein damage by myeloperoxidase in tracheal aspirates from preterm infants: association with adverse respiratory outcome.
abstract: Oxidative injury is implicated in the development of chronic lung disease in preterm infants with respiratory distress. However, direct evidence of a causal role is limited and the source of reactive oxidants has not been identified. We have previously shown that protein carbonyl levels in tracheal aspirates correlate positively with myeloperoxidase, suggesting that neutrophil oxidants could be the source of this protein injury. We have extended these observations by measuring 3-chlorotyrosine, a specific biomarker of the neutrophil oxidant, hypochlorous acid, in tracheal aspirate proteins (144 samples) from 69 infants with birth weight <1500 g. 3-Chlorotyrosine levels were higher in these infants than in larger infants without respiratory distress (median 83 compared with 13 micromol/mol tyrosine). They correlated strongly with myeloperoxidase activity (correlation coefficient 0.75, p < 0.0001) and to a lesser extent with protein carbonyls. 3-Chlorotyrosine levels (at 1 wk after birth) correlated negatively with birth weight or gestational age. They were significantly higher in infants who developed chronic lung disease (oxygen requirement at 36 wk postmenstrual age) than in those who did not (median 88 and 49 micromol/mol tyrosine, respectively) and correlated with days of supplemental oxygen. 3-Chlorotyrosine was also significantly higher in infants who had lung infection or were Ureaplasma urealyticum positive. Our results are the first evidence that chlorinated proteins are produced in the lungs of premature infants and that they are higher in infection. The higher 3-chlorotyrosine levels in infants who develop chronic lung disease suggest that neutrophil oxidants contribute to the pathology of this disease.
authors.affiliation: Department of Pathology, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand.
authors.forename: I Hendrikje
authors.initials: IH
authors.lastname: Buss
authors.forename: Revathy
authors.initials: R
authors.lastname: Senthilmohan
authors.forename: Brian A
authors.initials: BA
authors.lastname: Darlow
authors.forename: Nina
authors.initials: N
authors.lastname: Mogridge
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kettle
authors.forename: Christine C
authors.initials: CC
authors.lastname: Winterbourn
mesh_terms: D015415:Biomarkers; D002908:Chronic Disease; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism*; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism* / Q000382:microbiology; D014132:Trachea / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D016869:Ureaplasma Infections / Q000378:metabolism; D016990:Ureaplasma urealyticum
chemical_list: D015415:Biomarkers; D014443:Tyrosine; D009195:Peroxidase; C087259:3-chlorotyrosine