Eosinophil-selective binding and proapoptotic effect in vitro of a synthetic Siglec-8 ligand, polymeric 6 '-sulfated sialyl Lewis X

Sherry A. Hudson, Nicolai V. Bovin, Ronald L. Schnaar, Paul R. Crocker, Bruce S. Bochner

    Research output: Contribution to journalArticle

    60 Citations (Scopus)

    Abstract

    The lectin Siglec-8 (sialic acid-binding, immunoglobulin-like lectin), which is selectively expressed on eosinophil surfaces and regulates eosinophil survival, preferentially binds to the glycan 6'-sulfo-sialyl Lewis X (6'-sulfo-sLe(x)). Antibody engagement of Siglec-8 on eosinophils causes their apoptosis, suggesting that engagement of Siglec-8 with its natural glycan ligands in vivo may control allergic inflammation. We report that a soluble synthetic polymer displaying 6'-sulfo-sLe(x) glycan selectively binds to human eosinophils and human embryonic kidney 293 cells expressing Siglec-8. Binding was inhibited by anti-Siglec-8 antibody. In whole blood, eosinophils were the only leukocyte subtype to detectably bind polymeric 6'-sulfo-sLe(x). Interleukin-5-primed eosinophils underwent apoptosis when incubated with either anti-Siglec-8 monoclonal antibody or polymeric 6'-sulfo-sLe(x), although the glycan polymer was less effective. These data demonstrate that a soluble, multivalent glycan selectively binds to human eosinophils and induces their apoptosis in vitro and provide proof-of-concept that such a reagent could be used to selectively target eosinophils.

    Original languageEnglish
    Pages (from-to)608-612
    Number of pages5
    JournalJournal of Pharmacology and Experimental Therapeutics
    Volume330
    Issue number2
    Early online date19 May 2009
    DOIs
    Publication statusPublished - Aug 2009

    Keywords

    • Mast cells
    • Immunoglobulin superfamily
    • Apoptosis
    • Identification
    • Receptors
    • Induction
    • Mechanism
    • Roles

    Cite this