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To regenerate muscle, cellular garbage men must become builders
Date:9/22/2009

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/EBPβ, whose production increases in response to inflammation. They had genetically engineered mice in which this boost in C/EBPβ 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
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Contact: Lena Raditsch
lena.raditsch@embl.de
European Molecular Biology Laboratory
Source:Eurekalert  

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