When phagocytes let off steam
Rewiring the power plant of our cells supports “garbage burning” during inflammation.
New data from a research team at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) show that danger signals (so-called alarmins), which are released from damaged cells during inflammatory processes, enable a resolution of the inflammatory reaction and tissue regeneration by altering the metabolism of phagocytes (macrophages). By “rewiring” the intracellular power plants (mitochondria) in the phagocytes, they are protected from overload and can thus better dispose of components of damaged cells and thereby ensure the resolution of the inflammatory process. These results were recently published in the scientific journal “Immunity .
Inflammation is a natural and vital response of our immune system to danger signals and tissue damage. The inflammatory process helps to eliminate the respective trigger (e.g. bacteria) and to initiate repair mechanisms. Equally important, however, is a timely and coordinated end to this inflammatory reaction, otherwise there is a risk of developing a chronic inflammatory disease such as rheumatoid arthritis or Crohn’s disease. One of the key factors in the resolution of the inflammatory reaction is the hitherto insufficiently understood disposal of dangerous “hazardous waste” from damaged and dead cells, which can otherwise accumulate and cause renewed inflammation.
How inflammatory waste is disposed of
A research team led by Prof. Gerhard Krönke of the Medical Clinic 3 – Rheumatology and Immunology of the University Hospital Erlangen of the FAU (Director Prof. Georg Schett) has now succeeded in better understanding the underlying molecular mechanism. The research team investigated the function of phagocytes (macrophages) at the site of inflammation. These cells have the ability to take up large amounts of cellular waste and burn and dispose of its molecular components in their cellular power plants (mitochondria). The scientists were able to show that the danger signal interleukin-33, which is released from damaged cells, permanently alters the metabolism of macrophages in this process, which significantly increases their disposal capacity. Interleukin-33 regulates the function of the mitochondria in the macrophage, which are heavily stressed by the oversupply of waste in the inflammatory reaction and thus produce more harmful oxygen radicals. Interleukin-33 initiates a so-called “uncoupling” of these cellular power plants and thus protects them from overload. “In this way, the phagocytes are able to “let off steam”, so to speak, and to continue their feeding activity unhindered and efficiently despite great stress in the context of the resolution of inflammatory processes”, explains Maria Faas, the first author of the work that has just been published in the scientific journal “Immunity”.
Protection of power plants as a new therapeutic approach for inflammation
The findings of the FAU team could enable new therapeutic approaches for chronic inflammatory diseases. “By influencing the cellular metabolism of phagocytes and by selectively uncoupling their power plants, the resolution of inflammatory processes could be sustainably supported and accelerated” says Prof. Gerhard Krönke. Interestingly, active substances that favorably influence the cell metabolism of phagocytes are already known. The investigations and experiments were carried out as part of the DFG Collaborative Research Center SFB1181 “Checkpoints for the Resolution of Inflammation” and the DFG Research Unit FOR2886 PANDORA (Pathways triggering Autoimmunity and Defining Onset of early Reumatoid Arthritis). Maria Faas was additionally supported by a fellowship within the DFG Research Training Group 1660 (Key Signals of the Adaptive Immune Response).
Further information:
Prof. Dr. Gerhard Krönke
Tel.: 09131/85-34742
gerhard.kroenke@uk-erlangen.de