| The role of endothelial cell adhesion molecules P-selectin, E-selectin and intercellular adhesion molecule-1 in leucocyte recruitment induced by exogenous methylglyoxal. | |
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MedLine Citation:
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PMID: 22681228 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Methylglyoxal (MG) is a reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. In hyperglycaemic conditions, increased MG level has been linked to the development of diabetes and its vascular complications at the macrovascular and microvascular levels where inflammation plays a role. To study the mechanism of MG-induced inflammation in vivo, we applied MG locally to healthy mice and used intravital microscopy to investigate the role of endothelial cell adhesion molecules in MG-induced leucocyte recruitment in cremasteric microvasculature. Administration of MG (25 and 50 mg/kg) to the tissue dose-dependently induced leucocyte recruitment at 4.0-5.5 hr, with 84-92% recruited cells being neutrophils. Such MG treatment up-regulated the expression of endothelial cell adhesion molecules P-selectin, E-selectin, intercellular adhesion molecule-1, but not vascular cell adhesion molecule-1. Activation of the nuclear factor-κB signalling pathway contributed to MG-induced up-regulation of these adhesion molecules and leucocyte recruitment. The role of the up-regulated endothelial cell adhesion molecules in MG-induced leucocyte recruitment was determined by applying specific functional blocking antibodies to MG-treated animals and observing changes in leucocyte recruitment parameters. Our data demonstrate that the up-regulation of P-selectin, E-selectin and intercellular adhesion molecule-1 contributes to the increased leucocyte rolling flux, reduced leucocyte rolling velocity, and increased leucocyte adhesion, respectively. Our results reveal the role of endothelial cell adhesion molecules in MG-induced leucocyte recruitment in microvasculature, an inflammatory condition related to diabetic vascular complications. |
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Authors:
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Yang Su; Xi Lei; Lingyun Wu; Lixin Liu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Immunology Volume: 137 ISSN: 1365-2567 ISO Abbreviation: Immunology Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-08-06 Completed Date: 2012-10-30 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0374672 Medline TA: Immunology Country: England |
Other Details:
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Languages: eng Pagination: 65-79 Citation Subset: IM |
Copyright Information:
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© 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd. |
Affiliation:
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Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Blocking / immunology Cell Adhesion Cell Line E-Selectin / immunology, metabolism* Endothelial Cells / metabolism Endothelium, Vascular / immunology Intercellular Adhesion Molecule-1 / immunology, metabolism* Leukocyte Rolling / drug effects, immunology Leukocytes / physiology* Male Mice Mice, Inbred C57BL NF-kappa B / antagonists & inhibitors, metabolism Neutrophil Infiltration* Neutrophils / physiology* Nitriles / pharmacology P-Selectin / immunology, metabolism* Pyruvaldehyde / pharmacology* Signal Transduction Sulfones / pharmacology Up-Regulation Vascular Cell Adhesion Molecule-1 / immunology |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/3-(4-methylphenylsulfonyl)-2-propenenitrile; 0/Antibodies, Blocking; 0/E-Selectin; 0/NF-kappa B; 0/Nitriles; 0/P-Selectin; 0/Sulfones; 0/Vascular Cell Adhesion Molecule-1; 126547-89-5/Intercellular Adhesion Molecule-1; 78-98-8/Pyruvaldehyde |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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