Free Radical Research Group, Department of Pathology, University of Otago at Christchurch, Christchurch, New Zealand.
Free Radic Biol Med. 2010 Nov 15;49(9):1354-60. doi: 10.1016/j.freeradbiomed.2010.07.010. Epub 2010 Jul 18.
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.
我们旨在确定髓过氧化物酶（MPO）是否为囊性纤维化（CF）患儿气道中存在的主要过氧化物酶，并评估其产生的氧化剂，以及这些氧化剂是否与 CF 的临床特征相关。对 54 例 CF 患儿和 16 例非 CF 患儿进行支气管镜检查和支气管肺泡灌洗（BAL），以评估肺部感染和炎症情况。对 BAL 液进行 MPO、次氯酸的卤代酪氨酸作为指标、硫氰酸盐和蛋白质羰基的分析。MPO 是 CF 患儿 BAL 样本中唯一检测到的过氧化物酶，其浓度明显高于对照组。CF 组蛋白质中 3-氯酪氨酸和 3-溴酪氨酸的水平较高。它们与中性粒细胞和 MPO 相关。BAL 样本中硫氰酸盐的浓度低于 1μM。CF 患者的蛋白质羰基水平与 MPO 和卤代酪氨酸相关。MPO 和卤代酪氨酸的水平在感染尤其是铜绿假单胞菌感染的患儿中较高，且存在呼吸道症状。它们还与 Kanga 临床评分相关。我们的研究结果表明，MPO 在 CF 患儿的气道中产生次溴酸以及次氯酸，这些氧化剂参与 CF 的早期发病机制。
