04-21-2013, 11:28 AM
Cells previously known to create inflammation and generate fat have been discovered to be crucial in regenerating muscle tissue.
Scientists at UC San Francisco have performed the study. The experiments were performed on mice, and the results showed that an immune cell, which has been already substantially studies, called the eosinophil, has two more previously unknown beneficial roles. By clearing out cellular debris from damaged tissue it allows the new cells to re-grow and removes the threat from infection, and by teaming up with a type of cell that can make fat to instead trigger muscle regrowth it presents a key step in muscle regeneration.
The study was led by Ajay Chawla, MD, PhD, an associate professor of medicine at the UCSF Cardiovascular Research Institute. It showed that after eosinophils migrate to the site of injury, they work together with a progenitor cell, immature cells similar to stem cells, to power the formation of new muscle fibers. The progenitors are called the fibro/adipogenic cells (FAP), and they do not spin off muscle cells directly, instead serving as another key step in the activation of regeneration.
"Without eosinophils you cannot regenerate muscle," Chawla said.
FAP cells have previously been studied and are known for their roles in making fat, which occurs naturally as the body ages or experiences prolonged immobility. They also have been shown to make cells that form connective tissue. But the new study showed that FAP cells can also team up with eosinophils to make injured muscles regenerate and strengthen, rather than make them fatter, at least in mice.
In a cellular chain reaction, the team found that when eosinophils are at the site of muscle injury they secrete a molecule called IL-4, and the fibro/adipogenic progenitor cells respond by iniciating mitosis, increasing their numbers. And instead of becoming fat cells, as they were expected to, they react with the true muscle stem cells and trigger the regrowth and regeneration of muscle fibers.
"They wake up the cells in muscle that divide and form muscle fibers," Chawla stated.
Eosinophils normally help fight off bacteria and parasites, as do other immune cells, expecially of this subgroup, but eosinophils are more often considered in the maladaptive roles they have in allergies and other inflammatory reactions. Eosinophils comprise only a few percent of immune cells, being a relatively smaller subgroup compared to basophiles or neutrophiles.
The research team found that, even before active muscle repair incurs, the chain reaction initiated by eosinophils performs another necessary task, that is cleaning out the injury site of any debris or cellular garbage.
"Eosinophils, acting via FAPs, are needed for the rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues," Chawla said.
It has been thought until now that bigger and more common immune cells called macrophages, which are known to have large appetites and a propensity to ‘eat up’ debris in other injury or cell death scenarios are the ones tasked with cleaning up messes and remains within distressed or injured muscle tissue.
"Bites from venomous animals, many toxicants, and parasitic worms all trigger somewhat similar immune responses that cause injury. We want to know if eosinophils and FAPs are universally employed in these situations as a way to get rid of debris without triggering severe reactions such as anaphylactic shock." – said Chawla.
Other researchers working on this project are: postdoctoral fellow Jose E. Heredia, PhD; specialist Lata Mukundan, PhD; technician Francis Chen; Rahul Deo, MD, PhD, an assistant professor of medicine in residence; and Richard M. Locksley, MD, an immunologist and professor of medicine, Stanford researchers Thomas Rando, MD, PhD, and graduate student Alisa Mueller. The National Institutes for Health and the California Institute for Regenerative Medicine were the main founders of this research
Resources:
Jose E. Heredia, Lata Mukundan, Francis M. Chen, Alisa A. Mueller, Rahul C. Deo, Richard M. Locksley, Thomas A. Rando, Ajay Chawla. Type 2 Innate Signals Stimulate Fibro/Adipogenic Progenitors to Facilitate Muscle Regeneration. Cell, 2013
Scientists at UC San Francisco have performed the study. The experiments were performed on mice, and the results showed that an immune cell, which has been already substantially studies, called the eosinophil, has two more previously unknown beneficial roles. By clearing out cellular debris from damaged tissue it allows the new cells to re-grow and removes the threat from infection, and by teaming up with a type of cell that can make fat to instead trigger muscle regrowth it presents a key step in muscle regeneration.
The study was led by Ajay Chawla, MD, PhD, an associate professor of medicine at the UCSF Cardiovascular Research Institute. It showed that after eosinophils migrate to the site of injury, they work together with a progenitor cell, immature cells similar to stem cells, to power the formation of new muscle fibers. The progenitors are called the fibro/adipogenic cells (FAP), and they do not spin off muscle cells directly, instead serving as another key step in the activation of regeneration.
"Without eosinophils you cannot regenerate muscle," Chawla said.
FAP cells have previously been studied and are known for their roles in making fat, which occurs naturally as the body ages or experiences prolonged immobility. They also have been shown to make cells that form connective tissue. But the new study showed that FAP cells can also team up with eosinophils to make injured muscles regenerate and strengthen, rather than make them fatter, at least in mice.
In a cellular chain reaction, the team found that when eosinophils are at the site of muscle injury they secrete a molecule called IL-4, and the fibro/adipogenic progenitor cells respond by iniciating mitosis, increasing their numbers. And instead of becoming fat cells, as they were expected to, they react with the true muscle stem cells and trigger the regrowth and regeneration of muscle fibers.
"They wake up the cells in muscle that divide and form muscle fibers," Chawla stated.
Eosinophils normally help fight off bacteria and parasites, as do other immune cells, expecially of this subgroup, but eosinophils are more often considered in the maladaptive roles they have in allergies and other inflammatory reactions. Eosinophils comprise only a few percent of immune cells, being a relatively smaller subgroup compared to basophiles or neutrophiles.
The research team found that, even before active muscle repair incurs, the chain reaction initiated by eosinophils performs another necessary task, that is cleaning out the injury site of any debris or cellular garbage.
"Eosinophils, acting via FAPs, are needed for the rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues," Chawla said.
It has been thought until now that bigger and more common immune cells called macrophages, which are known to have large appetites and a propensity to ‘eat up’ debris in other injury or cell death scenarios are the ones tasked with cleaning up messes and remains within distressed or injured muscle tissue.
"Bites from venomous animals, many toxicants, and parasitic worms all trigger somewhat similar immune responses that cause injury. We want to know if eosinophils and FAPs are universally employed in these situations as a way to get rid of debris without triggering severe reactions such as anaphylactic shock." – said Chawla.
Other researchers working on this project are: postdoctoral fellow Jose E. Heredia, PhD; specialist Lata Mukundan, PhD; technician Francis Chen; Rahul Deo, MD, PhD, an assistant professor of medicine in residence; and Richard M. Locksley, MD, an immunologist and professor of medicine, Stanford researchers Thomas Rando, MD, PhD, and graduate student Alisa Mueller. The National Institutes for Health and the California Institute for Regenerative Medicine were the main founders of this research
Resources:
Jose E. Heredia, Lata Mukundan, Francis M. Chen, Alisa A. Mueller, Rahul C. Deo, Richard M. Locksley, Thomas A. Rando, Ajay Chawla. Type 2 Innate Signals Stimulate Fibro/Adipogenic Progenitors to Facilitate Muscle Regeneration. Cell, 2013
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