Description
Siglec-8, also known as SAF2, is a single-pass transmembrane CD33 subfamily receptor selectively expressed on human eosinophils and mast cells. Capable of exhibiting cell-type dependent inhibitory activity, siglec-8 has a N-terminal V-set Ig domain containing a sialoglycan binding site that forms strong interactions with the carboxylate group in sialic acid for ligation. In its cytoplasmic domain, siglec-8 has an immunoreceptor tyrosine-based inhibitory motif (ITIM) thought to be critical for downstream signaling and function. Engagement of Siglec-8 on cytokine-primed eosinophils promotes cell death through generation of reactive oxygen species. In contrast, siglec-8 engagement on mast cells inhibits cellular activation and mediator release. Siglec-8 agonist antibodies are currently under investigation for treatment of allergic and inflammatory diseases involving mast cells and eosinophils