Critical Role of Methylglyoxal and AGE in Mycobacteria-Induced Macrophage Apoptosis and Activation

• Published in: PloS one Vol. 1; no. 1
• Main Authors: Rachman, Helmy, Kim, Nayoung, Ulrichs, Timo, Baumann, Sven, Pradl, Lydia, Eddine, Ali Nasser, Bild, Matthias, Rother, Marion, Kuban, Ralf-Juergen, Lee, Jong Seok, Hurwitz, Robert, Brinkmann, Volker, Kosmiadi, George A, Kaufmann, Stefan HE
• Format: Journal Article
• Language: English
• Published: 01.01.2006
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0000029.

Apoptosis and activation of macrophages play an important role in the host response to mycobacterial infection involving TNF- alpha as a critical autocrine mediator. The underlying mechanisms are still ill-defined. Here, we demonstrate elevated levels of methylglyoxal x28; MGx29; , a small and reactive molecule that is usually a physiological product of various metabolic pathways, and advanced glycation end products x28; AGEx29; during mycobacterial infection of macrophages, leading to apoptosis and activation of macrophages. Moreover, we demonstrate abundant AGE in pulmonary lesions of tuberculosis x28; TBx29; 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.