Siglec-8 and Siglec-F: Inhibitory receptors on eosinophils, basophils, and mast cells

Background: Sialic acid binding immunoglobulin (Ig)-like lectins (Siglecs) are a family of inhibitory surface receptors expressed primarily by leukocytes. Among these, Siglec-8 is exclusively expressed on human eosinophils, mast cells and basophils. Its closest functional paralog in the mouse Is Siglec-E The function of these receptors on these cells is just now being examined. Methods/Data base: Various in vitro experiments involving purified human cells, cells grown from CD34+ precursors, cell lines, and in vivo mouse models are being employed along with specific anti-Siglec antibodies to define signaling function. Functional glycomic approaches are being used to screen for candidate glycan ligands for these Siglecs. Results: Siglec-8 or Siglec-F engagement on eosinophils by antibodies induces apoptosis in vitro. Siglec-8 engagement on human mast cells by antibodies does not induce apoptosis but does inhibit mediator release induced via Fc epsilon RI activation. Administration of Siglec-F antibodies to eosinophilic mice reduces circulating and tissue eosinophil levels. Screening using Siglec-8 and Siglec-F-Ig fusion proteins has identified a common glycan ligand, namely NeuAc alpha 2-3(6-O-sulfo)Gal beta 1-4[Fuc alpha 1-3]GlcNAc, also referred to as 6'-sulfo-sLe(x). Conclusions: Ongoing work on Siglec-8, and its paralog Siglec-F, has potential for identifying new therapeutic approaches for the treatment of diseases characterized by increased numbers of, or mediators from, eosinophils, basophils, and mast cells.