TAURINE MODULATION OF HYPOCHLOROUS ACID-INDUCED LUNG EPITHELIAL-CELL INJURY IN-VITRO - ROLE OF ANION TRANSPORT
TAURINE MODULATION OF HYPOCHLOROUS ACID-INDUCED LUNG EPITHELIAL-CELL INJURY IN-VITRO - ROLE OF ANION TRANSPORT
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DOI：
10.1172/jci117013
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发表时间：
1994-02-01
影响因子：
15.9
通讯作者：
MARTEL, M
中科院分区：
文献类型：
--
作者：
CANTIN, AM;BILODEAU, G;MARTEL, M
囊性纤维化患者的气道分泌物中发现含有高浓度的牛磺酸，在急性呼吸恶化期间抗生素治疗会降低牛磺酸浓度。牛磺酸与HOCl/OCl-的摩尔比为1：1，导致诱导对猫肺上皮细胞系AKD的细胞毒性所需的HOCl/OCl-量增加10倍。虽然DMSO保护细胞免受HOCl/OCl-介导的损伤，但等摩尔浓度的牛磺酸与HOCl/OCl-的存在阻止DMSO保护细胞和巯基免受氧化，表明牛磺酸氯胺的形成。光谱性质证实了一氯胺和二氯胺的形成。无氯缓冲液，DIDS，和低温（4摄氏度）保护细胞免受牛磺酸/HOCl/OCl-，表明牛磺酸氯胺通过阴离子转运途径的摄取是诱导细胞毒性所必需的。摩尔过量的牛磺酸通过减少牛磺酸二氯胺和增加毒性较小的牛磺酸一氯胺的形成来抑制细胞毒性。我们的结论是，牛磺酸可以保护肺上皮细胞通过转换HOCl/OCl-阴离子单氯胺，但牛磺酸二氯胺可以通过依赖于上皮细胞阴离子转运的机制，对呼吸道上皮细胞有毒。
Airway secretions of cystic fibrosis patients were found to contain high concentrations of taurine, which decreased with antibiotic therapy during acute respiratory exacerbations. Taurine, in a 1:1 molar ratio with HOCl/OCl-, caused a 10-fold increase in the amount of HOCl/OCl- needed to induce cytotoxicity to the cat lung epithelial cell line, AKD. Although DMSO protected cells against HOCl/OCl--mediated injury, the presence of an equimolar concentration of taurine with HOCl/OCl- prevented DMSO from protecting cells and sulfhydryl groups against oxidation, suggesting the formation of taurine chloramines. Spectral properties confirmed the formation of monochloramines and dichloramines. Chloride-free buffer, DIDS, and low temperature (4 degrees C) each protected the cells against taurine/HOCl/OCl-, indicating that taurine chloramine uptake through anion transport pathways was required to induce cytotoxicity. A molar excess of taurine inhibited cytotoxicity, by decreasing taurine dichloramines and increasing the formation of less toxic taurine monochloramines. We conclude that taurine can protect lung epithelial cells by converting HOCl/OCl- to anionic monochloramines, but that taurine dichloramines can be toxic to respiratory epithelial cells through mechanisms that depend upon epithelial cell anion transport.