A Cologne-based research team has found that the metabolism of mitochondria, the energy providers of cells, in macrophages coordinates wound healing to a significant degree. Macrophages belong to white blood cells and are also called scavenger cells. Professor Dr. Sabine Eming and his collaborators and colleagues from the CECAD Center of Excellence for Research on Aging at the University of Cologne have shown that wound macrophages undergo different metabolic programs during tissue repair, which are necessary to support the successive phases of skin reconstruction after an injury. The article “Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing” was published in Cell metabolism.
In the human body, macrophages can assume different states of activation. As pro-inflammatory macrophages in the early phase of wound healing, they kill bacteria or viruses and initiate a protective defense response. Late healing repair macrophages support the resolution of inflammation so that tissue can build up and balance can be restored. An unresolved question in macrophage biology is what signals are required for the transition from inflammatory macrophages to restorative macrophages. In the new study, Eming, senior physician in the department of dermatology and venereology and research group leader at CECAD and the Cologne Center for Molecular Medicine (CMMC), and his team demonstrated a functional link between tissue repair, the cell metabolism and the activation and function of tissue repairing macrophages. Changes in mitochondrial metabolism are the critical control mechanism for the various functions of macrophages during early and late wound healing.
In an animal model, scientists studied the metabolism of macrophages in early and late healing states. They discovered that the metabolism of sugar in the early phase is not sufficient for productive repair. Using single-cell sequencing, the team found that an early-stage macrophage subpopulation metabolizes reactive oxygen radicals produced in the mitochondria as a byproduct of cellular respiration. Eming and his team were able to show for the first time that the benefit of reactive oxygen-containing molecules in early wound macrophages is essential for ensuring blood vessel growth and therefore rapid healing. In contrast, macrophages use a different type of mitochondrial stromal exchange mediated by specific receptors (IL-4Ra) for their anti-inflammatory and restorative functions in the late phase of wound healing.
“Based on our results, it will be very interesting to understand whether disrupted mitochondrial stress in cells of the immune system contributes to aberrant inflammatory responses in the skin and wound healing disease states,” said Eming. “It will also be exciting to see whether pharmacological intervention in mitochondrial stress responses provides therapeutic benefit and facilitates repair of injured tissue.”
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