New Anti-allergy Drugs May Kill Eosinophils But Only Stun Mast Cells

Researchers have found the while eosinophils are killed by the apoptosis pathway triggered by activation of the membrane protein Siglec-8, mast cells do not die, but their release of inflammatory agents is inhibited.

Mast cells are large cells found in connective and fatty tissue that are often capable of amoeboid movement. They release substances such as leukotrienes, histamine, and heparin during allergic reactions and as part of the inflammation response. The action of mast cells is important in fighting infection; however, excessive mast cell activity is a hallmark of allergic reactions and asthma attacks.

Investigators from Johns Hopkins University (Baltimore, MD, USA) had previously shown that antibody activation of the surface protein Siglec-8 (sialic acid–binding immunoglobulin-like lectin) was toxic for the eosinophil class of immune cells. In the current study, they sought to find what effect this activation would have on mast cells.
Results published in the November 26, 2007, online edition of the Journal of Allergy and Clinical Immunology revealed a very different response of mast cells towards Siglec-8 activation. "We were surprised to see that these cells just sat there happily in their Petri dishes and lived on,” said senior author Dr. Bruce Bochner, professor of allergy and clinical immunology at Johns Hopkins University.

Siglec-8 activation failed to induce human mast cell apoptosis. However, pre-incubation of mast cells with Siglec-8 monoclonal antibodies significantly inhibited histamine and prostaglandin D2 release, Ca++ flux, and anti-IgE–evoked contractions of human bronchial rings.

These results suggest that it would be worthwhile to develop a drug that would have the dual effect of blocking or reducing allergic reactions by killing eosinophils and preventing mast cells from releasing their substances. "Both of these effects could make allergic diseases and asthma less severe,” said Dr. Bochner. "It is an intriguing approach because there are no drugs that specifically target both these cell types.”


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