It's hardly The Art of War. In what seems like a counterproductive effort, the immune system's first line of defense sets up a barricade to block the next wave of defenders, as shown by Ravi Rao, Francis Luscinskas (Harvard Medical School, Boston, MA), and colleagues.
The first immune cells to arrive at injured tissues are usually neutrophils. These cells transmigrate through the endothelial cells lining the vessel wall and release granules full of proteases that chew up the damaged tissue or infectious agents. Now, one of these proteases, called elastase, is shown to act on endothelial cells to deter the entry of later-arriving T cells.
Elastase hindered T cell transmigration by cleaving and inactivating the vessel-bound chemokine SDF-1α, which guides T cell migration on the vessel wall to entry sites. “When we started,” says Luscinskas, “we thought the neutrophils might enhance chemokine activities at the blood vessel wall, where more white blood cells are destined to transmigrate. But the opposite is true.” By closing the door on T cells, neutrophils might prevent potentially dangerous overactive immune responses.
Although protease inhibitors are abundant in the blood stream, plasma did not improve T cell entry. Elastase may be protected from the inhibitors by the neutrophil cell body, which physically seals off plasma inhibitors from accessing the space between the neutrophil and endothelium.