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Galectin mediated tethering and arrest of neutrophils under shear flow conditions
Department of Laboratory Medicine, Division of Microbiology, Immunology and Glycobiologi, Lund University, Lund, Sweden.
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Department of Laboratory Medicine, Division of Microbiology, Immunology and Glycobiologi, Lund University, Lund, Sweden.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

According to the conventional wisdom leukocyte recruitment to an inflammatory site is initiated by selectin mediated capture and rolling along the activated endothelium. The galectins are members of another family oflectins with affinity for ß-galactosides. Expressed on endothelial cells, galectin-1 and galectin-3 have been proposed to mediate cell-cell interactions during inflammation and tumor cell metastasis, and hence act as an alternative to selectins/integrins under certain circumstances. To begin testing this hypothesis, we examined the interaction of neutrophils -with a galectin-1 or galectin-3 coated surface under shear flow conditions. Both galectins were found to trigger neutrophil arrest in a dose and carbohydrate dependent manner at coating concentrations of ≥ 200 nM, and 1 dynes/cm2 wall shear stress. While, galectin-3 mediated neutrophil arrest was immediate, galectin-1 triggered a brief period of tethering before arrest. Rapidly following arrest neutrophils spread onto the galectin-coated surface. Cell spreading was accompanied by a redistribution of actin filaments, from an initial even staining with FITC-phalloidin to a more peripheral distribution in spread cells. These data suggest that galectin-1 and galectin-3 may act as adhesion molecules capturing and arresting neutrophils at sites knovvn to be less dependent on selectins and ß2integrins. They behave in part like selectins in capturing the neutrophils, but also like the integrins in triggering firm adhesion and cell spreading.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-81863OAI: oai:DiVA.org:liu-81863DiVA: diva2:556116
Available from: 2012-09-24 Created: 2012-09-24 Last updated: 2012-09-24Bibliographically approved
In thesis
1. Carbohydrate dependent adhesion of leukocytes and the role of fucosyltransferase VII
Open this publication in new window or tab >>Carbohydrate dependent adhesion of leukocytes and the role of fucosyltransferase VII
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Galectins, E-and P-selectins are carbohydrate-binding proteins that are up regulated at inflammatory lesions. Selectins expressed ou the activated endothelium mediate transient binding to leukocyte ligands that require sequential action of α 2,3-sialyltransferases and a 1,3-fucosyltransferases. ln leukocytes α1,3 fucosyltransferase VII adds fucose to α 2,3- sialylated lactosarnine acceptors in the final step of the biosynthesis of the selectin binding epitope sialyl Lewis x.

The finding of low sialyl Lewis x expression in polymorphonuclear leukocytes from a patient with ulcerative colitis led to the discovery of a missense mutation (G329A) in the human gene coding for α1,3 fucosyltransferase VII, FUT7. Studies including enzymatic and immunochemical analysis oftransfected cell lines and isolated polymorphonuclear leukocytes from patients confirmed that this mutation impair the ability of α1,3 fucosyltransferase VII to synthesize sialyl Lewis x. The frequency of the mutation were measured in a mixed Swedish population and found to be -1 %. One individual carrying the FUT7-G329A mutation homozygously was identified. This individual suffered from ulcer disease, noninsulin-dependent diabetes, osteoporosis, spondyloarthrosis, and Sjögren's syndrome, but the relationship between disease and the mutation is not established.

Studies using an in vitro flow chamber assay showed that transfected B-lymphoma cells and Epstein-Barr virus transformed B cells only transcribing FUT7-G329A were not able to interact with E-selectin during flow whereas polymorphonuclear leukocytes from the FUT7-G329A homozygous individual interacted well with both P- and E selectin during flow. The mRNA level of the fucosyltransferase IV coding gene, FUT4, was found to be elevated in the homozygous individual, which resulted in elevated levels ofthe CD65s epitope. However, transfected B-lymphoma cells and Epstein- Barr virus transformed cells did not show a similar elevation of FUT4 mRNA. In in vitro studies galectin-1 and- 3 were observed to be able to recruit polymorphonuclear leukocytes during flow. This thesis gives further insight into the molecular mechanisms leading to carbohydrate dependent dynamic adhesion between polymorphonuclear leukocytes and lectins during inflammation.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2003. 41 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 762
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25551 (URN)9999 (Local ID)91-7373-204-4 (ISBN)9999 (Archive number)9999 (OAI)
Public defence
2003-03-28, Berzeliussalen, Universitetssjukhuset, 13:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-09-24Bibliographically approved

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Bengtson, PerPåhlsson, Peter

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