April 2001

From Washington University School of Medicine

Molecule that guides nerve cells also directs immune cells

St. Louis, April 19, 2001 — 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."

Wu JY, Feng L, Park H-T, Havlioglu N, Wen L, Tang H, Bacon KB, Jiang Z, Zhang X, Rao Y. The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors. Nature, April 19, 2001.

Funding from the National Institutes of Health supported this research.












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