Tuesday, 18 October 2016

Mitochondrial Dysfunction Prevents Repolarization of Inflammatory Macrophages


Jan Van den Bossche, Jeroen Baardman, Natasja A. Otto, Saskia van der Velden, Annette E. Neele, Susan M. van den Berg, Rosario Luque-Martin, Hung-Jen Chen, Marieke C.S. Boshuizen, Mohamed Ahmed, Marten A. Hoeksema, Alex F. de Vos, Menno P.J. de Winther

Macrophages are types of white blood cell. They engulf and digest bodies which do not possess the correct protein markers which mark healthy cells. Whilst these cells play a crucial role in immunity, their dysfunction is associated with a number of auto-immune diseases such as asthma and rheumatoid arthritis. Macrophages exist in a spectrum of states, ranging from pro-inflammatory (M1) to anti-inflammatory (M2). In this study, the authors wished to investigate the mechanisms which prevent the transition from M1 to M2, so that we may better understand the mechanisms of inflammation.

Previous studies have shown that M1 cells are reliant upon glycolysis whereas M2 cells use mitochondrial oxidative phosphorylation (OXPHOS). These modes of energy production have also been associated with promoting the activation of these macrophage states. The authors find here that when macrophages are induced (using LPS + IFN-γ) to become M1 (pro-inflammatory) cells, this process inhibits OXPHOS. The signal (IL-4) which induces M2 (anti-inflammatory) cells cannot reverse this suppression of OXPHOS, and so they remain trapped in the pro-inflammatory state. The authors found that nitric oxide production by M1 cells, which is used as an antimicrobial mechanism and inhibits mitochondrial function, prevents the ability of M1 macrophages to be reprogrammed as non-inflammatory M2 cells.

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