Venglarik Charles J, Giron-Calle Julio, Wigley Amanda F, Malle Ernst, Watanabe Nobuo, Forman Henry Jay
Department of Environmental Health Sciences, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA.
J Appl Physiol (1985). 2003 Dec;95(6):2444-52. doi: 10.1152/japplphysiol.00002.2003. Epub 2003 Sep 26.
In chronic inflammatory diseases of the airways, such as cystic fibrosis, hypochlorous acid (HOCl) generated by neutrophils is involved in airway injury. We examined the effects of HOCl on 16HBE14o- bronchial epithelial cells by bolus addition or by generation with glucose oxidase plus myeloperoxidase. HOCl produced both carbonyl formation of a discreet number of proteins and modification of surface targets that were recognized by an antibody raised against HOCl-modified protein. Bolus or enzymatically generated HOCl decreased transepithelial resistance, but surprisingly bolus HOCl also increased short-circuit current. Glutathione in lung epithelial lining fluid is an excellent scavenger of HOCl; however, glutathione content is lower in cystic fibrosis epithelial lining fluid due to deficient glutathione transport to the apical side of bronchial-tracheal epithelial cells (Gao L, Kim KJ, Yankaskas JR, and Forman HJ. Am J Physiol Lung Cell Mol Physiol 277: L113-L118, 1999). We found that alteration of the GSH content of apical fluid above 16HBE14o- cells was protective because all HOCl-induced changes were delayed or eliminated by exogenous glutathione within the physiological range. Extrapolating this to cystic fibrosis suggests that HOCl can alter cell function without destruction but that elevating glutathione could be protective.
在气道慢性炎症性疾病中，如囊性纤维化，中性粒细胞产生的次氯酸（HOCl）参与气道损伤。我们通过一次性添加或用葡萄糖氧化酶加髓过氧化物酶生成HOCl来研究其对16HBE14o -支气管上皮细胞的影响。HOCl既导致了一定数量蛋白质的羰基化形成，也导致了表面靶点的修饰，这些靶点可被针对HOCl修饰蛋白产生的抗体识别。一次性添加或酶促生成的HOCl均降低了跨上皮电阻，但令人惊讶的是，一次性添加HOCl还增加了短路电流。肺上皮衬液中的谷胱甘肽是HOCl的优良清除剂；然而，由于谷胱甘肽向气管支气管上皮细胞顶端侧的转运不足，囊性纤维化上皮衬液中的谷胱甘肽含量较低（高L、金KJ、扬卡斯卡斯JR和福尔曼HJ。《美国生理学杂志：肺细胞与分子生理学》277：L113 - L118，1999）。我们发现，16HBE14o -细胞上方顶端液中谷胱甘肽含量的改变具有保护作用，因为在生理范围内，所有HOCl诱导的变化都被外源性谷胱甘肽延迟或消除。由此推断到囊性纤维化，表明HOCl可在不破坏细胞的情况下改变细胞功能，但提高谷胱甘肽水平可能具有保护作用。
