Novel Polymer Destroys Eosinophils and Reduces the Inflammatory Response

Allergy specialists have found that a synthetic polysaccharide could mimic the action of a monoclonal antibody and bind to an eosinophil surface lectin (sugar binding protein) in a fashion that triggered death of the cells with a subsequent reduction in overall immune inflammatory activity.

The lectin Siglec-8 (sialic acid-binding, immunoglobulin-like lectin), which is selectively expressed on eosinophil surfaces and regulates eosinophil survival, preferentially binds to the glycan 6′-sulfo-sialyl Lewis X (6′-sulfo-sLe X). Sialyl Lewis X, also known as sialyl Le X and SLe X, is a tetrasaccharide carbohydrate that is usually attached to O-glycans on the surface of certain granulocytes and is known to play a vital role in cell-cell recognition processes. Sialyl Lewis X is one of the most important blood group antigens and is displayed on the terminus of glycolipids that are present on the cell-surface.
Investigators at Johns Hopkins University (Baltimore, MD, USA) prepared a soluble synthetic polymer displaying 6′-sulfo-sLe X glycan. They found that this polymer selectively bound to human eosinophils and human embryonic kidney 293 cells expressing Siglec-8. Binding was inhibited by anti-Siglec-8 antibody. In whole blood, eosinophils were the only leukocyte subtype to bind the polymer.

Further results published in the August 2009 issue of the Journal of Pharmacology and Experimental Therapeutics revealed that when working with pure cultures of eosinophils, the polymer killed about 65% of the eosinophils in about 72 hours. It was, however, not as effective as a specific monoclonal antibody, which killed up to 90% of the cells in 24 hours.

"This is initial proof that delivering the sugar through a polymer can give you the desired result of selectively engaging Siglec-8 and killing eosinophils, but we still have a long way to go,” said senior author Dr. Bruce S. Bochner, professor of allergy and clinical immunology at Johns Hopkins University. "The trick is that you need to engage several clusters of Siglec-8 on each cell at once to trigger cell death. You are not going to be able to do that with individual sugar molecules in solution.”

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