TAURINE CHLORAMINE INHIBITS THE SYNTHESIS OF NITRIC-OXIDE AND THE RELEASE OF TUMOR-NECROSIS-FACTOR IN ACTIVATED RAW 264.7 CELLS
TAURINE CHLORAMINE INHIBITS THE SYNTHESIS OF NITRIC-OXIDE AND THE RELEASE OF TUMOR-NECROSIS-FACTOR IN ACTIVATED RAW 264.7 CELLS
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DOI：
10.1002/jlb.54.2.119
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发表时间：
1993-08-01
影响因子：
5.5
通讯作者：
SCHULLERLEVIS, G
中科院分区：
文献类型：
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作者：
PARK, E;QUINN, MR;SCHULLERLEVIS, G
牛磺酸在大多数哺乳动物组织中含量很高，包括那些能产生大量氧化剂的组织。牛磺酸对NO2、臭氧、博莱霉素和胺碘酮引起的细支气管损伤有保护作用。牛磺酸通过依赖卤化物的髓过氧化物酶系统氯化形成牛磺酸氯胺(Tau-Cl)，并在生理条件下降低HOCl的毒性。尽管NO及其代谢产物NO2-和NO3-被认为是氧化剂暴露所致组织损伤的主要介质，但包括肿瘤坏死因子(TNF)在内的细胞因子也参与其中。我们用重组干扰素-γ(50U/ml)和脂多糖(10ug/ml)激活RAW 264.7细胞，观察牛磺酸-氯对NO产生和肿瘤坏死因子释放的影响。NO以亚硝酸根形式与Griess试剂反应后用分光光度法测定，肿瘤坏死因子用ELISA法测定。0.5 mM的Tau-Cl对NO和TNF释放的抑制率分别为47%和43%。Tau-Cl通过依赖于能量、温度和Na+的摄取系统被主动转运到RAW 264.7细胞中。竞争实验表明，Tau-Cl与牛磺酸的吸收体系不同。此外，活化的RAW 264.7细胞胞液中的NO合成酶活性被牛磺酸-氯预处理不可逆地抑制。我们证明了Tau-Cl抑制激活的巨噬细胞产生NO和TNF，并提出了补充牛磺酸可以保护组织免受氧化剂诱导的组织损伤的机制。
Taurine is present in high concentrations in most mammalian tissues, including those that prodigiously produce oxidants. Taurine protects against bronchiolar damage induced by NO2, ozone, bleomycin, and amiodarone. Taurine is chlorinated to form taurine chloramine (Tau-Cl) by the halide-dependent myeloperoxidase system and, under physiological conditions, reduces HOCl toxicity. Although NO and its metabolites, NO2- and NO3-, are thought to be major mediators of tissue damage resulting from oxidant exposure, cytokines, including tumor necrosis factor (TNF), are also involved. We examined the effects of Tau-Cl on NO production and TNF release by using RAW 264.7 cells activated with recombinant interferon-gamma (rIFN-gamma; 50 U/ml) and lipopoly-saccharide (LPS; 10 mug/ml). NO was measured spectrophotometrically as NO2- after reaction with Griess reagent and TNF was measured by ELISA. Tau-Cl (0.5 mM) inhibits NO and TNF released into the medium by 47% and 43%, respectively. Tau-Cl is actively transported into RAW 264.7 cells by an uptake system that is energy, temperature, and Na+ dependent. Competition experiments demonstrate that the uptake system for Tau-Cl is distinct from that for taurine. In addition, the NO synthase activity of cytosolic preparations from activated RAW 264.7 cells is irreversibly inhibited by pretreatment with Tau-Cl. We demonstrate that Tau-Cl inhibits production of NO and TNF by activated macrophages and suggest a mechanism through which taurine supplementation may protect against oxidant-induced tissue damage.