Mitochondrial Dysfunction Prevents Repolarization of Inflammatory Macrophages.

By J. van den Bossche, J. Baardman, N. A. Otto, Saskia van der Velden, A. Neele, S. M. van den Berg, Rosario Luque-Martin, Hung-Jen Chen, Marieke C. S. Boshuizen, Mohamed Ahmed and 3 more. Cell Reports, 2016

880 citations recorded by the source corpus.

Macrophages are innate immune cells that adopt diverse activation states in response to their microenvironment. Editing macrophage activation to dampen inflammatory diseases by promoting the repolarization of inflammatory (M1) macrophages to anti-inflammatory (M2) macrophages is of high interest. Here, we find that mouse and human M1 macrophages fail to convert into M2 cells upon IL-4 exposure in vitro and in vivo. In sharp contrast, M2 macrophages are more plastic and readily repolarized into an inflammatory M1 state. We identify M1-associated inhibition of mitochondrial oxidative phosphorylation as the factor responsible for preventing M1→M2 repolarization. Inhibiting nitric oxide production, a key effector molecule in M1 cells, dampens the decline in mitochondrial function to improve metabolic and phenotypic reprogramming to M2 macrophages. Thus, inflammatory macrophage activation blunts oxidative phosphorylation, thereby preventing repolarization. Therapeutically restoring mitochondrial function might be useful to improve the reprogramming of inflammatory macrophages into anti-inflammatory cells to control disease.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/02189b737b421baa6929dcf1cb626f078d326bf9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. F. Munari
2. R. Sánchez-Rodríguez
3. Tommaso Scolaro
4. A. Viola
5. Alessandra Castegna

Citations in the corpus

• The Metabolic Signature of Macrophage Responses (2019, background): “Most importantly, NO prevents M1 to M2 repolarization, since the blockade of iNOS gives to M1 macrophages the ability to repolarize into M2, when exposed to IL-4 after LPS + IFN-γ treatment (120).”