Excerpt: Researchers have the first evidence that
cues that guide migrating nerve cells also direct white blood
cells called leukocytes, which have to find their way to inflamed,
infected or damaged areas of the body. The study is reported in
the April 19 issue of Nature.
"This similarity between the immune system and nervous
system might suggest new therapeutic approaches to immune system
disorders such as inflammation and autoimmune diseases," says Yi
Rao, Ph.D., an associate professor of anatomy and neurobiology at
Washington University School of Medicine in St. Louis.
This study was a collaboration between the School of
Medicine and Baylor College of Medicine. Rao and Jane Y. Wu,
Ph.D., an associate professor of pediatrics and of molecular
biology and pharmacology, led the Washington University teams.
Lili Feng, Ph.D., led the Baylor team.
After a cell is born, it navigates to its destination,
guided by signals from other molecules already in place.
Researchers have found that the nervous system uses molecules that
attract migrating cells, molecules that stop cell migration and
molecules that push cells away. But so far, only attractive
molecules have been identified in the immune system.
Neurons take minutes or hours to migrate to their
destinations, whereas leukocytes migrate within seconds. Even so,
Rao and colleagues wanted to determine whether migrating
leukocytes and neurons use similar mechanisms for finding their
ways.
"These experiments were carried out to address the question
whether there is mechanistic conservation between the two
systems," Rao says.
His group studied a protein called Slit, a known repellent
in neuronal migration. Two of the three known Slit proteins also
have been found in organs other than the brain.
The researchers simulated leukocyte migration in a dish,
using a molecule known to attract immune cells. When they added
human Slit protein (hSlit2) to the dish as well, fewer cells
migrated. They repeated the procedure in the presence of a
bacterial product also known to attract leukocytes. Again, hSlit2
inhibited cell migration. However, it did not inhibit other
functions of the bacterial product.
The team then determined whether Robo-a receptor that
enables Slit to act on nerve cells-plays a similar role in the
immune system. They had previously made a fragment of Robo which
blocks the normally full-length Robo protein. When this blocker
was added to the dish, Slit no longer inhibited leukocyte
migration. So Robo and a receptor on the cells appeared to be
competing for Slit. "These results suggest that Slit also is
likely to act through a Robo-like receptor on leukocytes to
inhibit their migration," Rao says.
He and his colleagues also are trying to find out whether
Slit can actively repel leukocytes and whether other neuronal
guidance cues influence immune cell migration.
This study bridges the gap between two previously
independent fields-immunology and neurology-and highlights the
need for collaboration. "This kind of research could have been
done several years ago," Rao says. "But we all get used to
addressing questions in our own fields. This study shows what
happens if we venture out and collaborate with scientists in other
fields."
