Researchers at Cytel Corp., who have found a second moleculegoverning white blood cell traffic into tissue, report that themolecule acts through the company's identified carbohydratemarker on cells. Competitors, however, say the findings arestill controversial.
Last year the San Diego company reported on a carbohydrate onthe surface of neutrophil white blood cells that latches onto amarker on blood vessels called endothelial leukocyte adhesionmolecule-1 (ELAM-1). The interaction governed by ELAM-1between blood vessel cells and neutrophils leads to pathologicinflammation. Rival Glycomed Inc. of Alameda, Calif., has alsocharacterized a related, but structurally distinct,carbohydrate from human neutrophils that bind to ELAM-1.
Both companies are trying to design anti-inflammatory drugswith minimal side effects, based on carbohydrates. Thesesugar-based drugs could be used to selectively treat suchchronic inflam-matory diseases as psoriasis and rheumatoidarthritis, as well as septic shock, without interfering with theentire immune system.
Now Cytel reports that a second cell-adhesion molecule, GMP-140, also binds with its identified carbohydrate to initiatewhite cell migration through blood vessels into tissues.Results appear in this week's Proceedings of the NationalAcademy of Sciences.
The significance of locating the binding partner for GMP-140is that this adhesion molecule governs extremely rapidinflammatory responses. A drug that could interfere withwhite cell infiltration mediated by GMP-140 could, forexample, prevent the reperfusion injury seen in heart attackpatients. ELAM-1, in contrast, mediates slower inflammatoryresponses, such as those seen in arthritis.
"This clearly broadens the possibilities for a carbohydrate-based therapeutic" in inflammatory diseases, said HowardGrey, vice president of research at privately held Cytel.
Brian Brandley, section head of bioscreening at Glycomed, saidthat other research groups have not achieved Cytel's resultswith GMP-140, possibly because different assays were used."We haven't confirmed any interaction (with the carbohydrateand GMP-140), but we're saying, 'let's wait and see,' " Brandleytold BioWorld.
-- Roberta Friedman, Ph.D. Special to BioWorld
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