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Role of glycosylation in regulation of E-selectin expression on endothelial cells
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
1997 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Endothelial cells located on the vessel walls play an important role in inflammation. In response to cytokines or other inflammatory mediators endothelial cells will express different cell adhesion molecules that are involved in binding of circulating leukocytes to the endothelium. The initial binding involves interactions between the selectin family of adhesion molecules and carbohydrate epitopes. This interaction induces rolling of leukocytes in postcapillary venules. After rolling, protein-protein interactions between immunoglobulin super family members on the endothelial surface and integrins on the leukocytes provide firm adhesion and diapedesis into the inflamed tissue.

The expression of E-selectin is strictly regulated during the inflammation process. Cytokine activation of endothelial cells induces E-selectin synthesis, maximum surface expression is reached 4-6 hours after stimulation and then declines to basal level within 24 hours. It is likely that several factors are involved in this tight regulation. Since E-selectin is highly glycosylated the aim of this study was to investigate the role of N-glycosylation in E-selectin expression and function. Eselectin expression on cultured human umbilical vein endothelial cells (HUVEC) was studied using flow cytometry, cell ELISA and immunoprecipitation analyses. Modification of glycosylation was obtained by culturing HUVEC in presence of soluble glycosylation inhibitors.

Our results showed that E-selectin is highly glycosylated with N-linked, complex type oligosaccharides. N-linked glycosylation of E-selectin was found to be important for the level of cell surface expression and turn-over time. However, defect glycosylation did not affect its binding properties as revealed in a static cell binding assay.

Mixtures of cytokines can produce a different expression of E-selectin. For example, when a mixture of TNF-α and IFN-γ are used to stimulate HUVEC an enhanced and prolonged expression of E-selectin is obtained compared to when HUVEC are stimulated with TNF-α alone. Our results showed that this effect could be blocked by monensin, which is an inhibitor of trans-Golgi network processing. This again indicated a role for post translational modification in regulation of E-selectin expression.

During inflammation a multitude of cytokines and inflammatory mediators are involved in defining and regulating the immune response. It is known that these mediators also affect glycosylation machinery in several cells. The present study suggests that these glycosylation alterations may have a direct consequence by regulating the expression of cell adhesion molecules.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1997. , 40 p.
Linköping Studies in Health Sciences. Thesis, ISSN 1100-6013 ; 30
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-28270Local ID: 13019ISBN: 91-7871-791-4OAI: diva2:249074

Papers, included in licentiate theses, are not registered and included in the posts from 1999 and earlier.

Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2013-07-08

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Strindhall, Jan
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