Kettle Anthony J, Chan Timothy, Osberg Iris, Senthilmohan Revathy, Chapman Anna L P, Mocatta Tessa J, Wagener Jeffrey S
Free Radical Research Group, Department of Pathology, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand.
Am J Respir Crit Care Med. 2004 Dec 15;170(12):1317-23. doi: 10.1164/rccm.200311-1516OC. Epub 2004 Oct 1.
Cystic fibrosis (CF) is characterized by considerable oxidative stress. However, it is not known whether oxidative stress is an important feature early in this disease. We have investigated a group of infants and young children with CF to establish whether oxidants are produced in their airways. Bronchoalveolar lavage fluid (BALF) was assayed for myeloperoxidase as a measure of neutrophilic inflammation, and 3-chlorotyrosine as a biomarker of the potent oxidant hypochlorous acid, which is formed by myeloperoxidase. Protein carbonyls were also measured as a nonspecific indicator of reactive oxidant production. Myeloperoxidase and 3-chlorotyrosine levels in BALF from children with CF were 10- and fivefold higher, respectively, than in disease control subjects. There was a strong correlation between myeloperoxidase and 3-chlorotyrosine. Myeloperoxidase levels were fourfold higher in children with infections in their airways. Median protein carbonyls were elevated by only twofold compared with disease control subjects, but some children had extremely high levels of protein oxidation. We conclude that hypochlorous acid is produced early in CF and that it is a candidate for precipitating the fatal decline in lung function associated with this disease. Also, there must be other sourcesof oxidants because protein carbonyls were not related to either inflammation or infection.
囊性纤维化（CF）的特征是存在相当程度的氧化应激。然而，氧化应激是否是该疾病早期的一个重要特征尚不清楚。我们对一组患有CF的婴幼儿进行了研究，以确定其气道中是否会产生氧化剂。检测支气管肺泡灌洗液（BALF）中的髓过氧化物酶以衡量中性粒细胞炎症，检测3-氯酪氨酸作为强效氧化剂次氯酸的生物标志物，次氯酸由髓过氧化物酶形成。还测量了蛋白质羰基作为活性氧化剂产生的非特异性指标。CF患儿BALF中的髓过氧化物酶和3-氯酪氨酸水平分别比疾病对照受试者高10倍和5倍。髓过氧化物酶与3-氯酪氨酸之间存在很强的相关性。气道有感染的患儿髓过氧化物酶水平高4倍。与疾病对照受试者相比，蛋白质羰基的中位数仅升高了2倍，但一些患儿的蛋白质氧化水平极高。我们得出结论，次氯酸在CF早期就会产生，并且它是导致与该疾病相关的致命肺功能下降的一个因素。此外，肯定还有其他氧化剂来源，因为蛋白质羰基与炎症或感染均无关。
