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Researchers find new way to block destructive rush of immune cells
Date:1/14/2008

r Vaccine Biology and Immunology at the Medical Center, and lead author of the article. Good examples include when our immune system attacks our own cells, or rejects a lifesaving transplant or clogs our blood vessels by mistake. The problem is that past, system-wide attempts that block all integrin activation, like the multiple sclerosis drug Tysabri, shut down not only unwanted inflammation in one locale, but also vital immune defenses elsewhere, leaving patients vulnerable to infection.

The Great Migration

Two mechanisms make cell migration, or programmed directional movement, possible. The first, called chemotaxis, tells the cell which direction to move in. Cell surface proteins sense and follow chemicals and molecules they are attracted to toward wherever those attractants are most concentrated. T cells, named after the thymus (T) where they mature, move toward the byproducts of bacteria and viruses.

The second migratory mechanism is propulsion. In between infections and injuries, inactive T cells ride along with the bloodstream. T cells realize when they pass by part of a blood vessel wall close to the site of an injury or infection. Integrins on their surfaces unfold and grab onto key proteins on the surface of blood vessel wall cells (e.g. ICAM), resisting the surrounding blood flow. The T cells then pass through the vessel wall, and once outside the bloodstream, crawl along the tissue scaffolding toward the site of injury.

In a T cell at rest, integrins are distributed evenly over the entire surface of the T cell. When the cell gets ready to move, however, activated integrins cluster on the leading edge of the cell in the direction the cell wants to move in. They bind to their counterpart adhesion proteins like ICAM on the surface that the T cell is moving across. The T cell then contracts using its cell skeleton to pull itself over the leading edge integrins. Finally, the integrins on the trailing edge of the
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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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