Ilyas, Rebecca, Wallis, Russell, Soilleux, Elizabeth J., Townsend, Paul, Zehnder, Daniel, Tan, Bee K., Sim, Robert B., Lehnert, Hendrik, Randeva, Harpal S. and Mitchell, Daniel A. (2011) High glucose disrupts oligosaccharide recognition function via competitive inhibition : a potential mechanism for immune dysregulation in diabetes mellitus. Immunobiology, Vol.216 (No.1-2). pp. 126-131. doi:10.1016/j.imbio.2010.06.002

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Abstract

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 & 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.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Diabetes -- Complications, Oligosaccharides, Lectins, Immune response -- Regulation
Journal or Publication Title:	Immunobiology
Publisher:	Elsevier
ISSN:	0171-2985
Official Date:	January 2011
Dates:	Date Event January 2011 Published
Volume:	Vol.216
Number:	No.1-2
Page Range:	pp. 126-131
DOI:	10.1016/j.imbio.2010.06.002
Status:	Peer Reviewed
Access rights to Published version:	Restricted or Subscription Access
Funder:	University of Warwick, Research Councils UK (RCUK), Wellcome Trust (London, England)
Grant number:	077400 (Wellcome)

Data sourced from Thomson Reuters' Web of Knowledge

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