|
HOUSTON -- (February 21, 2008) -- A gene that "wakes up" the blood
system's stem cells in times of stress also plays an important role in
protecting against infection, said researchers from Baylor College of
Medicine in Houston, the National Institute of Allergy and Infectious
Disease and Duke University Medical School in a report that appears in
the journal Cell Stem Cell.
When Dr. Margaret Goodell, professor of pediatrics and director of
BCM's Stem Cells and Regeneration (STaR) Center, and her colleagues
infected mice that lacked the gene interferon-inducible GTPase Lrg-47
with a bacteria akin to tuberculosis, they found that stem cells did
not initiate the process of making blood cells to protect against the
infection.
Stress response
"It suggests that this gene might have a role in normal blood
production, but its main role is in stress response," she said. "It's
really involved in recovery from a toxic drug or infection or
regenerating a blood system after a bone marrow transplant."
It makes sense that a serious infection with a pathogen or
disease-causing organism could require that stem cells rally to
generate new blood cells to fight against the invading organisms.
"In the mice with the defective gene, the stem cells could not wake
up," said Goodell. "It is the first time anyone has a shown a link
between infection and activating stem cells."
"You probably have to activate the stem cells to make all your blood cells. This gene might be a link in that system," she said.
"What was surprising was that this gene was regulated by interferon
gamma," she said. "These proteins are well known because they regulate
the immune system."
Surprise finding
Finding the interferon-inducible GTPase Lrg-47 in stem cells was a
surprise, she said. "Maybe it is a way of the immune system talking to
stem cells."
Collaborating with the NIAID team helped answer the question. They
had bred mice to lack the gene and shown that these mice died of an
infection that normal mice could easily control. The team in Bethesda,
Maryland, noted that the mice had low blood counts.
They shared their mice with the BCM team who looked at the animals'
stem cell biology. The mice with the defective gene had stem cells that
did not function well. Under normal conditions, they could make blood.
However, when stressed by a chemical or disease-causing organism that
attacked the blood cells, the stem cells did not recover quickly.
When Goodell and her colleagues tried to do a bone marrow transplant with the mice, it did not work.
"They were almost completely incapable of regenerating the blood system in another mouse," she said.
In the future, she said, she and her colleagues want to study why
this gene has such an impact on stem cells. It will also help delineate
the role of interferons in the cell.
Others who took part in this work include Drs. Carl G. Feng and Alan
Sher of NIAID, David C. Weksberg of BCM and Dr. Gregory A. Taylor of
Duke.
Funding for this work comes from the National Institutes of Health and the Leukemia and Lymphoma Society.
The article is available at http://www.cellstemcell.com/content/article/abstract?uid=PIIS193459090700224X&highlight=goodell.
Powered by AkoComment 2.0! |
