| High glucose disrupts oligosaccharide recognition function via competitive inhibition: a potential mechanism for immune dysregulation in diabetes mellitus. | |
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MedLine Citation:
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PMID: 20674073 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Diabetic complications include infection and cardiovascular disease. Within the immune system, host-pathogen and regulatory host-host interactions operate through binding of oligosaccharides by C-type lectin. A number of C-type lectins recognise oligosaccharides rich in mannose and fucose - sugars with similar structures to glucose. This raises the possibility that high glucose conditions in diabetes affect protein-oligosaccharide interactions via competitive inhibition. Mannose-binding lectin, soluble DC-SIGN and DC-SIGNR, and surfactant protein D, were tested for carbohydrate binding in the presence of glucose concentrations typical of diabetes, via surface plasmon resonance and affinity chromatography. Complement activation assays were performed in high glucose. DC-SIGN and DC-SIGNR expression in adipose tissues was examined via immunohistochemistry. High glucose inhibited C-type lectin binding to high-mannose glycoprotein and binding of DC-SIGN to fucosylated ligand (blood group B) was abrogated in high glucose. Complement activation via the lectin pathway was inhibited in high glucose and also in high trehalose - a nonreducing sugar with glucoside stereochemistry. DC-SIGN staining was seen on cells with DC morphology within omental and subcutaneous adipose tissues. We conclude that high glucose disrupts C-type lectin function, potentially illuminating new perspectives on susceptibility to infectious and inflammatory disease in diabetes. Mechanisms involve competitive inhibition of carbohydrate binding within sets of defined proteins, in contrast to broadly indiscriminate, irreversible glycation of proteins. |
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Authors:
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Rebecca Ilyas; Russell Wallis; Elizabeth J Soilleux; Paul Townsend; Daniel Zehnder; Bee K Tan; Robert B Sim; Hendrik Lehnert; Harpal S Randeva; Daniel A Mitchell |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-01 |
Journal Detail:
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Title: Immunobiology Volume: 216 ISSN: 1878-3279 ISO Abbreviation: Immunobiology Publication Date: 2011 Jan-Feb |
Date Detail:
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Created Date: 2010-11-29 Completed Date: 2011-07-18 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 8002742 Medline TA: Immunobiology Country: Netherlands |
Other Details:
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Languages: eng Pagination: 126-31 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier GmbH. All rights reserved. |
Affiliation:
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Clinical Sciences Research Institute, University of Warwick, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipose Tissue
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pathology Bacterial Infections Binding, Competitive / immunology Cell Adhesion Molecules / genetics, metabolism* Complement Pathway, Mannose-Binding Lectin Dendritic Cells / immunology, metabolism*, pathology Diabetes Complications Glucose / chemistry, metabolism* Host-Pathogen Interactions Humans Immunity, Innate Immunohistochemistry Immunomodulation Lectins, C-Type / genetics, metabolism* Mannose-Binding Lectin / genetics, immunology, metabolism* Oligosaccharides, Branched-Chain / chemistry, immunology, metabolism* Receptors, Cell Surface / genetics, metabolism* Stereoisomerism Surface Plasmon Resonance |
| Grant Support | |
ID/Acronym/Agency:
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077400//Wellcome Trust; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/CLEC4M protein, human; 0/Cell Adhesion Molecules; 0/DC-specific ICAM-3 grabbing nonintegrin; 0/Lectins, C-Type; 0/Mannose-Binding Lectin; 0/Oligosaccharides, Branched-Chain; 0/Receptors, Cell Surface; 50-99-7/Glucose |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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