Identifying peroxidases and their oxidants in the early pathology of cystic fibrosis.
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.
Thomson
Eline
E
Free Radical Research Group, Department of Pathology, University of Otago at Christchurch, Christchurch, New Zealand.
Brennan
Siobhain
S
Senthilmohan
Revathy
R
Gangell
Catherine L
CL
Chapman
Anna L
AL
Sly
Peter D
PD
Kettle
Anthony J
AJ
Balding
Elizabeth
E
Berry
Luke J
LJ
Carlin
John B
JB
Carzino
Rosemary
R
de Klerk
Nick
N
Douglas
Tonia
T
Foo
Clara
C
Garratt
Luke W
LW
Hall
Graham L
GL
Harrison
Jo
J
Kicic
Anthony
A
Laing
Ingrid A
IA
Logie
Karla M
KM
Massie
John
J
Mott
Lauren S
LS
Murray
Conor
C
Parsons
Faith
F
Pillarisetti
Naveen
N
Poreddy
Srinivas R
SR
Ranganathan
Sarath C
SC
Robertson
Colin F
CF
Robins-Browne
Roy
R
Robinson
Philip J
PJ
Skoric
Billy
B
Stick
Stephen M
SM
Sutanto
Erika N
EN
Williamson
Elizabeth
E
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
D014443:Tyrosine; C118327:3-bromotyrosine; D009195:Peroxidase; C087259:3-chlorotyrosine