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

Jin P. Guo, Esra Nutku, Hidenori Yokoi, Ronald L. Schnaar, Nives Zimmermann, Bruce S. Bochner

Research output: Contribution to journalArticle

Abstract

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-F. 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 FcṘI 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 NeuAcα2-3(6-O-sulfo)Galβ 1-4[Fucα1-3]GlcNAc, also referred to as 6′-sulfo-sLex. 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.

Original languageEnglish (US)
Pages (from-to)54-59
Number of pages6
JournalAllergy and Clinical Immunology International
Volume19
Issue number2
DOIs
StatePublished - Mar 1 2007

    Fingerprint

Keywords

  • Siglec-8
  • Siglec-F

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this