title: Identifying peroxidases and their oxidants in the early pathology of cystic fibrosis.
abstract: We aimed to determine whether myeloperoxidase (MPO) is the main peroxidase present in the airways of children with cystic fibrosis (CF) and to assess which oxidants it produces and whether they are associated with clinical features of CF. Children with CF (n=54) and without CF (n=16) underwent bronchoscopy and bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. BAL fluid was analyzed for MPO, halogenated tyrosines as markers of hypohalous acids, thiocyanate, and protein carbonyls. MPO was the only peroxidase detected in BAL samples from children with CF and its concentration was markedly higher than in controls. Levels of 3-chlorotyrosine and 3-bromotyrosine in proteins were higher in the CF group. They correlated with neutrophils and MPO. The concentration of thiocyanate in BAL samples was below 1μM. Protein carbonyl levels correlated with MPO and halogenated tyrosines in patients with CF. Levels of MPO and halogenated tyrosines were higher in children with infections, especially Pseudomonas aeruginosa, and in the presence of respiratory symptoms. They also correlated with the Kanga clinical score. Our findings suggest that MPO produces hypobromous acid as well as hypochlorous acid in the airways of children with CF and that these oxidants are involved in the early pathogenesis of CF.
authors.affiliation: Free Radical Research Group, Department of Pathology, University of Otago at Christchurch, Christchurch, New Zealand.
authors.forename: Eline
authors.initials: E
authors.lastname: Thomson
authors.forename: Siobhain
authors.initials: S
authors.lastname: Brennan
authors.forename: Revathy
authors.initials: R
authors.lastname: Senthilmohan
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Gangell
authors.forename: Anna L
authors.initials: AL
authors.lastname: Chapman
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kettle
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Balding
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Berry
authors.forename: John B
authors.initials: JB
authors.lastname: Carlin
authors.forename: Rosemary
authors.initials: R
authors.lastname: Carzino
authors.forename: Nick
authors.initials: N
authors.lastname: de Klerk
authors.forename: Tonia
authors.initials: T
authors.lastname: Douglas
authors.forename: Clara
authors.initials: C
authors.lastname: Foo
authors.forename: Luke W
authors.initials: LW
authors.lastname: Garratt
authors.forename: Graham L
authors.initials: GL
authors.lastname: Hall
authors.forename: Jo
authors.initials: J
authors.lastname: Harrison
authors.forename: Anthony
authors.initials: A
authors.lastname: Kicic
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Laing
authors.forename: Karla M
authors.initials: KM
authors.lastname: Logie
authors.forename: John
authors.initials: J
authors.lastname: Massie
authors.forename: Lauren S
authors.initials: LS
authors.lastname: Mott
authors.forename: Conor
authors.initials: C
authors.lastname: Murray
authors.forename: Faith
authors.initials: F
authors.lastname: Parsons
authors.forename: Naveen
authors.initials: N
authors.lastname: Pillarisetti
authors.forename: Srinivas R
authors.initials: SR
authors.lastname: Poreddy
authors.forename: Sarath C
authors.initials: SC
authors.lastname: Ranganathan
authors.forename: Colin F
authors.initials: CF
authors.lastname: Robertson
authors.forename: Roy
authors.initials: R
authors.lastname: Robins-Browne
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Robinson
authors.forename: Billy
authors.initials: B
authors.lastname: Skoric
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Stick
authors.forename: Erika N
authors.initials: EN
authors.lastname: Sutanto
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Williamson
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation; D008297:Male; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D012141:Respiratory Tract Infections / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D014443:Tyrosine; C118327:3-bromotyrosine; D009195:Peroxidase; C087259:3-chlorotyrosine