Venketaraman Vishwanath, Dayaram Yaswant K, Amin Amol G, Ngo Richard, Green Renee M, Talaue Meliza T, Mann Jessica, Connell Nancy D
Department of Microbiology and Molecular Genetics. New Jersey Medical School National Tuberculosis Center, UMDNJ-New Jersey Medical School, 225 Warren Street, Newark, NJ 07103, USA.
Infect Immun. 2003 Apr;71(4):1864-71. doi: 10.1128/IAI.71.4.1864-1871.2003.
Reactive oxygen and nitrogen intermediates are important antimicrobial defense mechanisms of macrophages and other phagocytic cells. While reactive nitrogen intermediates have been shown to play an important role in tuberculosis control in the murine system, their role in human disease is not clearly established. Glutathione, a tripeptide and antioxidant, is synthesized at high levels by cells during reactive oxygen intermediate and nitrogen intermediate production. Glutathione has been recently shown to play an important role in apoptosis and to regulate antigen-presenting-cell functions. Glutathione also serves as a carrier molecule for nitric oxide, in the form of S-nitrosoglutathione. Previous work from this laboratory has shown that glutathione and S-nitrosoglutathione are directly toxic to mycobacteria. A mutant strain of Mycobacterium bovis BCG, defective in the transport of small peptides such as glutathione, is resistant to the toxic effect of glutathione and S-nitrosoglutathione. Using the peptide transport mutant as a tool, we investigated the role of glutathione and S-nitrosoglutathione in animal and human macrophages in controlling intracellular mycobacterial growth.
活性氧和氮中间体是巨噬细胞及其他吞噬细胞重要的抗菌防御机制。虽然活性氮中间体已被证明在鼠类系统的结核病控制中发挥重要作用，但其在人类疾病中的作用尚未明确确立。谷胱甘肽是一种三肽和抗氧化剂，在细胞产生活性氧中间体和氮中间体期间会大量合成。最近研究表明，谷胱甘肽在细胞凋亡中起重要作用，并调节抗原呈递细胞的功能。谷胱甘肽还以S-亚硝基谷胱甘肽的形式作为一氧化氮的载体分子。本实验室之前的研究表明，谷胱甘肽和S-亚硝基谷胱甘肽对分枝杆菌具有直接毒性。牛分枝杆菌卡介苗的一个突变菌株，在转运诸如谷胱甘肽等小肽方面存在缺陷，对谷胱甘肽和S-亚硝基谷胱甘肽的毒性作用具有抗性。利用该肽转运突变体作为工具，我们研究了谷胱甘肽和S-亚硝基谷胱甘肽在动物和人类巨噬细胞控制细胞内分枝杆菌生长中的作用。
