Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

To regenerate muscle, cellular garbage men must become builders

22.09.2009
Crucial role of macrophages in muscle regeneration uncovered by EMBL scientists

For scientists at the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy, what seemed like a disappointing result turned out to be an important discovery.

Their findings, published online this week in the journal Proceedings of the National Academy of Sciences (PNAS), provide conclusive proof that, when a muscle is injured, white blood cells called macrophages play a crucial role in its regeneration. The scientists also uncovered the genetic switch that controls this process, a finding that opens the door for new therapeutic approaches not only to sports injuries but also to diseases such as Duchenne muscular dystrophy.

Normally, macrophages – the white blood cells known for engulfing and eliminating bacteria and other infectious agents – are drawn to areas of injury. Once there, they act as garbage men, eliminating the dead cells and releasing pro-inflammatory factors, fending off infection. After clearing up the debris, macrophages stop releasing those pro-inflammatory factors, and start making anti-inflammatory factors that promote repair in the damaged area. This shift from clearing debris to promoting building is known as macrophage polarization, and Claus Nerlov, Nadia Rosenthal and colleagues proved that it is essential for muscles to regenerate properly.

“There seems to be this point of no return”, says Rosenthal: “if macrophages don’t make this switch, then the muscle won’t repair itself – you just end up with scar, instead of new tissue”.

Nerlov and his research group at EMBL were studying a protein called C/EBPâ, whose production increases in response to inflammation. They had genetically engineered mice in which this boost in C/EBPâ production was blocked, to see what effect this had on the development of the different cells involved in the immune system. To their dismay, the answer appeared to be ‘almost none’. The modified mice developed normally, and had normal blood cells – except their macrophages didn’t polarize. Although this result fell short of the scientists’ expectations of understanding how blood cells develop, it raised an interesting possibility in the context of Rosenthal’s research into muscle regeneration. If these mice could not repair muscle injuries properly, it would prove that macrophage polarization is indispensable for muscle regeneration. The two groups teamed up to investigate how the ability to respond to muscle injury was affected in mice whose C/EBPâ production boost had been blocked. Their findings proved that macrophages still migrated to the injured site and cleared the debris, but because they failed to make that all-important switch, the muscle didn’t repair properly, becoming scarred instead.

At a stroke, the EMBL scientists confirmed the importance of macrophages in repairing muscle tissue and discovered its genetic basis. Normally, inflammatory factors trigger an increase in C/EBPâ production, which in turn activates genes that cause the macrophage to polarize.

“From a medical point of view, it would seem that the trick to improve muscle repair is finding a way to increase C/EBPâ production and keep it high”, Nerlov concludes, adding “if we can now figure out exactly which key genes C/EBPâ controls, that will give us even more potential targets.”

As well as investigating the other steps on this molecular pathway, the scientists are currently studying a possible role for macrophage polarization in repairing heart muscle, with a view to better understanding and treating heart disease.

Source Article
Ruffell, D., Mourkioti, F., Gambardella, A., Kirstetter, P., Lopez, R. G., Rosenthal, N. & Nerlov, C. A CREB-C/EBPâcascade induces M2 macrophage-specific gene expression and promotes muscle injury repair, PNAS online Early Edition, 21-25 September 2009.
Lena Raditsch
Head of Communications
Office of Information and Public Affairs
European Molecular Biology Laboratory - EMBL
Meyerhofstr. 1
69117 Heidelberg
Germany
T: +49 6221 387 8125
F: +49 6221 387 8525
M:+49 151 14532784
lena.raditsch@embl.de

Lena Raditsch | EMBL
Further information:
http://www.embl.org

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>