NIH Research Matters
July 21, 2006
Probing the Body's Protective Inner Barriers
Between the blood and the tissues of all our organs from our brains, lungs and hearts to the organs of the immune system our bodies maintains a careful balance of immune cells, fluids and countless molecules. When that balance is disrupted, it can cause serious illness, such as when fluid accumulates in the lungs or when lymph organs release immune cells that attack the body's own tissues, as in multiple sclerosis and other autoimmune diseases. A team of experts funded by NIH has now developed a chemical tool that allows scientists to manipulate control of the passage of substances between these barriers. Altering the barriers between the blood and tissues may one day prove an effective way to prevent and treat illnesses of this kind.
The team of researchers, led by Dr. Hugh Rosen of The Scripps Research Institute, focused on the S1P1 receptor system. These receptors open and close molecular "gates" on biological barriers such as the lining of blood vessels, where the exchange of substances between blood and tissues occurs, and the tissues of lymph organs, which produce and regulate the passage of lymphocytes (the main cells of the immune system) into the bloodstream.
The researchers searched for published studies on compounds that block the S1P1 receptor and synthesized a chemical blocker of their own, hoping that it would promote the passage of substances through the barriers of the vascular and immune systems. Paired with a previously known activator of the S1P1 receptor to counter the effects of the chemical blocker, they went on to investigate the effects of these compounds in mice. They focused on two different biological barriers among the many on which S1P1 receptors are found: blood vessel walls and lymph organs. Their study was posted online July 9, 2006, in Nature Chemical Biology. The compound the researchers synthesized effectively blocked S1P1 receptors. Using the two chemical compounds together, the researchers were able to reversibly manipulate these molecular gates in living mice. They found, however, that the blood vessel and immune-system tissues differed in the levels of these compounds at which they responded a reminder of how complex a challenge it will be to develop therapeutic approaches using this strategy.
This new chemical probe is among the first developed by scientists working within NIH's Molecular Libraries Screening Centers Network (MLSCN). The MLSCN has established a collection of over 100,000 chemically diverse small molecules for use as chemical probes in basic research. This study is the latest to illustrate the success of this approach.
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Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.
NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.