Scientists at Johns Hopkins and their colleagues have developed sugar-coated polymer strands that selectively kill off cells involved in triggering aggressive allergy and asthma attacks. Their advance is a significant step toward crafting pharmaceuticals to fight these often life-endangering conditions in a new way.
For more than a decade, a team led by Bruce S. Bochner, M.D., director of the Division of Allergy and Clinical Immunology at the Johns Hopkins University School of Medicine, has studied a unique protein known as Siglec-8. This protein, whose name is an acronym for Sialic Acid-binding, Immunoglobulin-like LECtin number 8, is present on the surfaces of a few types of immune cells, including eosinophils, basophils and mast cells. These different cell types have diverse but cooperative roles in normal immune function and allergic diseases. When functioning correctly, they are a valuable aid to keeping the body healthy and infection-free. However, in allergic reactions and asthma attacks, the cells unleash an overwhelming response that typically harms the body more than it helps.
The researchers found in previous studies that when they bound antibodies that specifically target Siglec-8 to the protein on eosinophils, the cells promptly died, an effect that might be useful in stemming an allergy or asthma attack. Since producing antibodies can be expensive—a potential roadblock to using them as pharmaceuticals in the future—the researchers sought another way to activate this protein.
Several years ago, Bochner and his colleagues discovered an unusual sugar that could uniquely and selectively attach to and activate Siglec-8. "The trick is that you need to engage several clusters of Siglec-8 on each cell at once to trigger cell death. You're not going to be able to do that with individual sugar molecules in solution," Bochner says.
To accomplish this goal, the team developed soft, flexible polymer strands coated with the sugar, "like microscopic spaghetti candy," says Bochner.
Using cells genetically modified to produce Siglec-8 on their surfaces and cells without the protein, the researchers tested whether the polymer bound when applied to the cells. As expected, the polymer bound only to the cells that produced Siglec-8. Polymer strands without the sugar, or with different attached sugars, could not bind to the cells. Additionally, when the researchers pretreated Siglec-8-producing cells with antibodies that target the protein, the polymer couldn't attach, suggesting that it specifically targets Siglec-8 and not another protein on the cells.