Critical role of methylglyoxal and AGE in mycobacteria-induced macrophage apoptosis and activation.
Critical role of methylglyoxal and AGE in mycobacteria-induced macrophage apoptosis and activation.
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DOI：
10.1371/journal.pone.0000029
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发表时间：
2006-12-20
期刊：
影响因子：
3.7
通讯作者：
Kaufmann SH
中科院分区：
文献类型：
--
作者：
Rachman H;Kim N;Ulrichs T;Baumann S;Pradl L;Nasser Eddine A;Bild M;Rother M;Kuban RJ;Lee JS;Hurwitz R;Brinkmann V;Kosmiadi GA;Kaufmann SH
巨噬细胞的凋亡和活化在宿主对分枝杆菌感染的反应中起重要作用，TNF-α作为一种重要的自分泌介质。其基本机制仍然不明确。在这里，我们证明了甲基乙二醛（MG），一个小的和反应性的分子，通常是各种代谢途径的生理产物，和晚期糖基化终末产物（AGE）在分枝杆菌感染的巨噬细胞，导致细胞凋亡和激活的水平升高。此外，我们证明丰富的AGE在肺结核（TB）患者的肺部病变。MG处理的巨噬细胞的全局基因表达谱揭示了MG诱导的多种功能，包括细胞凋亡和免疫应答。我们的研究结果不仅为MG和AGE参与结核病提供了第一个证据，而且还为MG和AGE发挥关键作用的新型传染病干预策略奠定了基础。
Apoptosis and activation of macrophages play an important role in the host response to mycobacterial infection involving TNF-α as a critical autocrine mediator. The underlying mechanisms are still ill-defined. Here, we demonstrate elevated levels of methylglyoxal (MG), a small and reactive molecule that is usually a physiological product of various metabolic pathways, and advanced glycation end products (AGE) during mycobacterial infection of macrophages, leading to apoptosis and activation of macrophages. Moreover, we demonstrate abundant AGE in pulmonary lesions of tuberculosis (TB) patients. Global gene expression profiling of MG-treated macrophages revealed a diverse spectrum of functions induced by MG, including apoptosis and immune response. Our results not only provide first evidence for the involvement of MG and AGE in TB, but also form a basis for novel intervention strategies against infectious diseases in which MG and AGE play critical roles.
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