Defense or repair: How immune cells are controlled during wound healing


Date:
December 8, 2021
Source:
University of Cologne
Summary:
Scientists show a causal link between tissue repair, mitochondrial
metabolism, and the activation and function of macrophages
(scavenger cells).



FULL STORY ==========================================================================
A Cologne-based research team has discovered that the metabolism of mitochondria, the energy suppliers of cells, in macrophages coordinate
wound healing to a significant degree. Macrophages belong to the white
blood cells and are also known as scavenger cells. Professor Dr. Sabine
Eming and her collaborators and colleagues at the CECAD Cluster of
Excellence for Aging Research at the University of Cologne showed that
wound macrophages undergo different metabolic programs during tissue
repair, which are required to support the successive phases for skin reconstruction after injury. The article 'Mitochondrial metabolism
coordinates stage-specific repair processes in macrophages during wound healing' has now been published in Cell Metabolism.


==========================================================================
In the human body, macrophages can adopt different activation states. As
pro- inflammatory macrophages in the early phase of wound healing,
they kill bacteria or viruses and initiate a protective defense
response. Reparative macrophages of late wound healing support the
resolution of inflammation so that tissue can build up and equilibrium
can be restored. An unresolved question in macrophage biology is what
signals are required for the transition from inflammatory to reparative macrophages. In the new study, Eming, senior physician at the Department
of Dermatology and Venereology and research group leader at CECAD
and the Center for Molecular Medicine Cologne (CMMC), and her team
demonstrated a functional link between tissue repair, cell metabolism,
and the activation and function of tissue-repairing macrophages. Changes
in mitochondrial metabolism are the critical control mechanism for the different functions of macrophages during early and late wound healing.

In an animal model, the scientists studied the metabolism of
macrophages in the early and late wound healing states. They found
that sugar metabolism in the early phase is not sufficient to ensure
productive repair. Using single-cell sequencing, the team discovered
that a subpopulation of early-stage macrophages metabolizes reactive
oxygen radicals produced in mitochondria as a byproduct of cellular respiration. Eming and the team were able to show for the first time
that the benefit of the reactive oxygen-containing molecules in early
wound macrophages is essential to ensure the growth of blood vessels,
and thus timely healing. In contrast, macrophages use a different type of mitochondrial stromal exchange mediated by specific receptors (IL-4Ra)
for their anti-inflammatory and reparative functions in the late phase
of wound healing.

'Based on our results, it will be very interesting to understand whether disturbed mitochondrial stress in cells of the immune system contribute
to aberrant inflammatory responses in the skin and pathological wound
healing states,' said Eming. 'It will also be exciting to see if
pharmacologic intervention in mitochondrial stress responses provides therapeutic benefit and facilitates the repair of injured tissue.' ========================================================================== Story Source: Materials provided by University_of_Cologne. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Sebastian Willenborg, David E. Sanin, Alexander Jais, Xiaolei Ding,
Thomas Ulas, Julian Nu"chel, Milica Popović, Thomas MacVicar,
Thomas Langer, Joachim L. Schultze, Alexander Gerbaulet, Axel Roers,
Edward J.

Pearce, Jens C. Bru"ning, Aleksandra Trifunovic, Sabine A. Eming.

Mitochondrial metabolism coordinates stage-specific repair processes
in macrophages during wound healing. Cell Metabolism, 2021; 33
(12): 2398 DOI: 10.1016/j.cmet.2021.10.004 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211208123417.htm

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