Ligands for the beta-glucan receptor, Dectin-1, assigned using 'designer' microarrays of oligosaccharide probes (neoglycolipids) generated from glucan polysaccharides
Autor: | Ten Feizi, Siamon Gordon, Angelina S. Palma, Mark S. Stoll, Alexander M. Lawson, Yibing Zhang, Esther Díaz-Rodríguez, Júlia Costa, María Asunción Campanero-Rhodes, Wengang Chai, Gordon D. Brown |
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Rok vydání: | 2005 |
Předmět: |
beta-Glucans
Recombinant Fusion Proteins Saccharomyces cerevisiae Nerve Tissue Proteins Plasma protein binding Curdlan Biology Polysaccharide Ligands Biochemistry Cell Line chemistry.chemical_compound Mice Polysaccharides Animals Humans Secretion Lectins C-Type Molecular Biology Glucan Oligonucleotide Array Sequence Analysis chemistry.chemical_classification Macrophages Zymosan Membrane Proteins Cell Biology Oligosaccharide biology.organism_classification chemistry Glycolipids Oligonucleotide Probes Protein Binding |
Zdroj: | The Journal of biological chemistry. 281(9) |
ISSN: | 0021-9258 |
Popis: | Dectin-1 is a C-type lectin-like receptor on leukocytes that mediates phagocytosis and inflammatory mediator production in innate immunity to fungal pathogens. Dectin-1 lacks residues involved in calcium ligation that mediates carbohydrate-binding by classical C-type lectins; nevertheless, it binds zymosan, a particulate beta-glucan-rich extract of Saccharomyces cerevisiae, and binding is inhibited by polysaccharides rich in beta1,3- or both beta1,3- and beta1,6-linked glucose. The oligosaccharide ligands on glucans recognized by Dectin-1 have not yet been delineated precisely. It is also not known whether Dectin-1 can interact with other types of carbohydrates. We have investigated this, since Dectin-1 shows glucan-independent binding to a subset of T-lymphocytes and is involved in triggering their proliferation. Here we assign oligosaccharide ligands for Dectin-1 using the neoglycolipid-based oligosaccharide microarray technology, a unique approach for constructing microarrays of lipid-linked oligosaccharide probes from desired sources. We generate "designer" microarrays from three glucan polysaccharides, a neutral soluble glucan isolated from S. cerevisiae and two bacterial glucans, curdlan from Alcaligenes faecalis and pustulan from Umbilicaria papullosa, and use these in conjunction with 187 diverse, sequence-defined, predominantly mammalian-type, oligosaccharide probes. Among these, Dectin-1 binding is detected exclusively to 1,3-linked glucose oligomers, the minimum length required for detectable binding being a 10- or 11-mer. Thus, the ligands assigned so far are exogenous rather than endogenous. We further show that Dectin-1 ligands, 11-13 gluco-oligomers, in clustered form (displayed on liposomes), mimic the macromolecular beta-glucans and compete with zymosan binding and triggering of tumor necrosis factor-alpha secretion by a Dectin-1-expressing macrophage cell line. |
Databáze: | OpenAIRE |
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