A team of experts funded by the National Institutes of Health (NIH) has developed
a chemical tool that allows scientists to manipulate control of the passage of
substances through the barriers between blood and the tissues of every organ — from
the brain, lungs, and heart to the organs of the immune system. The passage of
substances, such as immune cells, water, and other fluids that occurs through
these barriers maintains a healthy balance between the blood and tissues; however,
serious illness may result when the balance is disrupted. Fluid may accumulate
in the lungs, for example, or lymph organs may inappropriately release immune
cells that attack the body's own tissues, as in multiple sclerosis and other
autoimmune diseases.
The study, conducted in living mice, focused on the S1P1 receptor system, a
mechanism that opens and closes molecular ?gates? on biological barriers, such
as the lining of blood vessels and barriers in the tissues of lymph organs. Researchers
showed that they could manipulate the mechanism with selective chemical compounds,
raising the possibility of finding ways to alter the mechanism for prevention
and treatment of illnesses. Together, the compounds act as a pair of chemical
probes that interact with the receptor in ways that enable researchers to explore
the receptor system's actions.
The probes will enable scientists to define medically important functions of
the S1P1 receptor system by seeing how biological barriers change — and
the physiological effects of those changes — when researchers alter the "set
point" at which the receptor goes into action. Results of the study will be published
on-line July 9, 2006, and in the August issue of Nature Chemical Biology.
The probe is among the first developed by scientists working within the Molecular
Libraries Screening Centers Network (MLSCN) initiative, part of the NIH Roadmap,
an enterprise designed to answer fundamental questions that are shared by many
fields of research and whose answers will lead to major progress in virtually
all of them. The MLSCN initiative, which was established in 2004, is guided by
two NIH institutes, the National Institute of Mental Health and the National
Human Genome Research Institute. Other chemical probes are likely to follow from
the initiative?s efforts, since its purpose is to develop such tools for the
scientific community.
"This chemical tool has implications for research on the brain, the lungs, the
heart; anywhere in the body that there are biological barriers which must be
crossed and whose dysfunction can result in illness," said NIH Director Elias
Zerhouni, M.D. "This is exactly the kind of fundamental finding the NIH Roadmap
was designed to generate, which scientists from here to academia to industry
can use to accelerate their research toward practical applications," he added.
Led by Hugh Rosen, MB.ChB., D. Phil., of The Scripps Research Institute, a team
of investigators focused on two different biological barriers, among the many
on which S1P1 receptors are found: capillary walls, where exchange of substances
between the blood and tissues occurs; and lymph organs, which produce and regulate
passage of lymphocytes, the main cells of the immune system, into the bloodstream.