When macrophages let off steam
Changes in cell metabolism protect macrophages from overloading and thus assist the resolution of inflammatory reactions
Date:
November 5, 2021
Source:
Friedrich-Alexander-Universita"t Erlangen-Nu"rnberg
Summary:
New data shows how inflammatory reactions can be resolved by
changes to the metabolism of macrophages. Danger signals released
by damaged cells during inflammation play a role during this
process. 'Rewiring' the mitochondria in the macrophages protects
them against overloading and can thus improve the way in which
parts of damaged cells are eliminated and resolve the inflammatory
reaction.
FULL STORY ==========================================================================
New data from a research team at Friedrich-Alexander-Universita"t
Erlangen- Nu"rnberg (FAU) shows how inflammatory reactions can be
resolved by changes to the metabolism of macrophages. Danger signals
released by damaged cells during inflammation play a role during this
process. 'Rewiring' the mitochondria in the macrophages protects them
against overloading and can thus improve the way in which parts of damaged cells are eliminated and resolve the inflammatory reaction. The results
were recently published in the journal Immunity.
========================================================================== Inflammation is a natural and vital response of our immune system to
danger signals and tissue damage. Inflammatory processes help the body
to eliminate the triggers, for example bacteria, and to initiate repair mechanisms.
Terminating this inflammatory reaction quickly and in a coordinated manner
is just as important, however, as otherwise there is a risk of developing chronic inflammatory conditions such as rheumatoid arthritis or Crohn's disease. One of the important factors for resolving the inflammatory
reaction is the elimination of damaged and dead cells, a process that
was not very well understood until now. New inflammation can occur if
these cells are allowed to accumulate.
How waste from inflammation is disposed of A research team led by
Prof. Gerhard Kro"nke at the Department of Medicine 3 - - Rheumatology
and Immunology at Universita"tsklinikum Erlangen has now succeeded in
gaining a better understanding of the fundamental molecular mechanisms involved. The researchers investigated the function of macrophages at
the site where inflammation occurs. These cells are capable of ingesting
large quantities of cellular waste and digesting and eliminating the
molecular components of this waste in their mitochondria, also referred
to as the powerhouse of the cell.
The scientists were able to demonstrate that the danger signal interleukin
33, which is released from damaged cells, triggers lasting changes to
the metabolism of macrophages, so that their waste disposal capacity significantly increases. The sheer quantity of waste produced during
the inflammatory reaction places the mitochondria under severe strain,
and they produce increased quantities of damaging oxygen radicals as
a result. Interleukin 33 regulates the function of the mitochondria
by initiating a process known as uncoupling in these cell components
and protecting them from overloading. 'This enables the macrophages to
'let off steam' and carry on ingesting waste without interruption despite
the heavy strain placed upon them, resolving the inflammation processes
as a result,' explains Maria Faas, lead author of the article recently published in the journal 'Immunity'.
Protection of mitochondria as a new approach for therapy for inflammation
The findings of the FAU team could pave the way for new approaches
for treating chronic inflammatory conditions. 'It may be possible to
accelerate and support the resolution of inflammatory processes in the
long term by influencing the cell metabolism of the macrophages and deliberately uncoupling their mitochondria,' explains Prof. Gerhard
Kro"nke. Interestingly, substances that positively influence the cell metabolism of macrophages have already been discovered. However, they
have not yet been approved for use in chronic inflammatory conditions and
must undergo further clinical trials. The investigations and experiments
were conducted as part of the DFG collaborative research centre CRC 1181 'Switching points for resolving inflammation' and the DFG research group FOR2886 PANDORA (Pathways triggering Autoimmunity and Defining Onset of
early Rheumatoid Arthritis). Maria Faas also received a scholarship as
part of the DFG research training group 1660 (Key signals of adaptive
immune response).
========================================================================== Story Source: Materials provided by Friedrich-Alexander-Universita"t_Erlangen-Nu"rnberg.
Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Maria Faas, Natacha Ipseiz, Jochen Ackermann, Stephan Culemann,
Anika
Gru"neboom, Fenja Schro"der, Tobias Rothe, Carina Scholtysek, Martin
Eberhardt, Martin Bo"ttcher, Philipp Kirchner, Cornelia Stoll,
Arif Ekici, Maximilian Fuchs, Meik Kunz, Benno Weigmann, Stefan
Wirtz, Roland Lang, Joerg Hofmann, Julio Vera, David Voehringer,
Alessandro Michelucci, Dimitrios Mougiakakos, Stefan Uderhardt,
Georg Schett, Gerhard Kro"nke.
IL-33-induced metabolic reprogramming controls the differentiation
of alternatively activated macrophages and the resolution of
inflammation.
Immunity, 2021; DOI: 10.1016/j.immuni.2021.09.010 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2021/11/211105150307.htm
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