title: Eosinophil-selective binding and proapoptotic effect in vitro of a synthetic Siglec-8 ligand, polymeric 6'-sulfated sialyl Lewis x.
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.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. bbochner@jhmi.edu.
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Hudson
authors.forename: Nicolai V
authors.initials: NV
authors.lastname: Bovin
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Schnaar
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crocker
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Bochner
mesh_terms: D015703:Antigens, CD / Q000097:blood / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000097:blood / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000097:blood / Q000378:metabolism; D002460:Cell Line; D004804:Eosinophils / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D037102:Lectins / Q000097:blood / Q000378:metabolism*; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D008024:Ligands; D009844:Oligosaccharides / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives
chemical_list: C086949:6'-sulfated sialyl Lewis x; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D051017:Apoptosis Regulatory Proteins; D018836:Inflammation Mediators; D037102:Lectins; D016256:Lewis X Antigen; D008024:Ligands; D009844:Oligosaccharides; C403967:SIGLEC8 protein, human; D000080506:Sialyl Lewis X Antigen