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 journalArticlepeer-review

64 Scopus citations

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-sLex). 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-sLex 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-sLex. Interleukin-5-primed eosinophils underwent apoptosis when incubated with either anti-Siglec-8 monoclonal antibody or polymeric 6′-sulfo-sLex, 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 (US)
Pages (from-to)608-612
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume330
Issue number2
DOIs
StatePublished - Aug 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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