The Enemy Within - Unexpected Cell Type Orchestrate Immune Turmoil in Flu - via ScienceNow

When a patient gets killed by a specially lethal kind of flu, as in the recent outbreaks of H1N1 or H5N1 (swine and avian) strains of flu virus, it might be the body's own defenses that make the final move. The flu and other infections can provoke so-called cytokine storms or immunological storms. One hallmark of these events is a surge of chemical messengers called cytokines and chemokines into tissues and the blood, promoting inflammation. Immune cells, including macrophages and natural killer cells, also flood the lungs. The combination can cause fatal disease with lung and other organs damage. Some flu strains might initiate more often these immune waves. For example, animal studies suggest that the Spanish flu virus (the one that killed millions in the 1918 epidemia) makes the immune system overaggressive. Cells that line the lungs and airways and the immune cells that move in after infection are responsible for cytokine storms—or at least that's what researchers thought.

A team led by chemical biologist Hugh Rosen and virologist Michael Oldstone of the Scripps Research Institute in San Diego, California, investigated the S1P pathway, a molecular control circuit that fine-tunes immune responses. The scientists gave influenza-infected rodents a compound that stimulates the S1P1 receptor. The treatment prevented a cytokine outburst and reduced movement of immune cells into the lungs. When the researchers looked after the cells in the lungs that carry the S1P1 receptor, they found that it occurs on endothelial cells, which line lymphatic and blood vessels, and on the white blood cells known as lymphocytes. To determine which of these two cell types controls the cytokine surge, the researchers tested the S1P1 receptor activator in genetic modified mice that lack lymphocytes. The compound also prevented the storms in these animals, suggesting that endothelial cells, not lymphocytes, orchestrate cytokine release. This fascinating finding opens a whole new avenue of research into flu and potentially many other infectious and inflammatory diseases, where endothelial cells may have a previously unknown important role.

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Surprising Cells Rein In Killer Flu - ScienceNOW - http://bit.ly/pe8PUo