Expression and Function of Siglec-8 in Human Eosinophils, Basophils, and Mast Cells

Siglec-8, the eighth member of the sialic acid-binding, immunoglobulin [Ig]-like lectin family, was initially discovered as a cell surface protein selectively expressed on human eosinophils. It is now know to also be expressed by mast cells and basophils. Siglec-8 engagement with specific antibodies causes apoptosis via caspase and mitochondrial-dependent pathways. For mast cells, inhibition of mediator release, but no apoptosis, is observed. Siglec-F is the closest mouse paralog to Siglec-8, and both selectively bind the sulfated glycan 6’-sulfo-sialyl Lewis X. Antibodies to Siglec-F reduce blood and tissue eosinophil numbers in vivo. This suggests that Siglec-8 may be a useful future therapeutic target for allergic and other eosinophilic disorders.