Studding the surfaces of white blood cells like the one in this photo, protein molecules called L-selectins help these immune system cells perform their tasks, such as traveling to the site of an impending infection to fend off microbes. But the body�s process of recruiting immune cells to combat injury or infection has its own shortcomings--in the act of responding to such crises, immune cells spill their toxic contents and inevitably damage normal cells in the process. The result is inflammation and pain. Developing means to quash inflammation is therefore an important goal, and indeed is the target of an ongoing, multibillion-dollar pharmaceutical effort.
A few years ago, NIGMS grantee Dr. Laura Kiessling of the University of Wisconsin, Madison had a hunch that causing L-selectin molecules on immune cells to cluster together might send a signal to the cells� clean-up crews to clip the molecules from the cell surface. By doing so, the cells would lose critical "docking sites" that normally render the cells capable of sticking to each other--a key step in setting off an inflammatory response.
The hunch was correct. Members of a new class of synthetic sugar molecules called "neoglycopolymers" can in fact perform this trick, causing L-selectin molecules first to cluster and then to slough off the cell surface. Neoglycopolymers are simple to make and act to halt inflammatory processes in a distinctly different way than do existing anti-inflammatory drugs, such as aspirin or ibuprofen. While the latter compounds block signaling molecules inside the cell, neoglycopolymers prevent cells from touching each other in the first place. Dr. Kiessling�s research should yield valuable insights into cellular processes that hinge upon cell migration, including inflammation, the spread of cancer throughout the body, and perhaps even the way in which bacteria go about their business of infecting people.
Gordon EJ, Sanders WJ, Kiessling LL. Synthetic ligands point to cell surface strategies. Nature 1998;392:30-1.
Reporters may call the NIGMS Office of Communications and Public Liaison at (301) 496-7301 to obtain the name of a scientist in the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry who can comment on this work.
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8/9/2018 5:46 PM
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