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Formation of the proteolytically active tissue factorFVIIa complex leads to enhanced PDGF-BB-stimulated chemotaxis and IL-8 and TNF-α production in monocytes
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-91006OAI: oai:DiVA.org:uu-91006DiVA: diva2:163568
Available from: 2003-10-30 Created: 2003-10-30 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Monocytes, Tissue Factor and Heparin-coated Surfaces: Clinical and Experimental Studies
Open this publication in new window or tab >>Monocytes, Tissue Factor and Heparin-coated Surfaces: Clinical and Experimental Studies
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. Heparin coating of the CPB circuit is shown to improve the biocompatibility of the surface. The biological effects of a new heparin surface, the Corline Heparin Surface (CHS), prepared according to a new principle, have been studied.

The CHS used during coronary artery bypass grafting with CPB in sixty patients prevented adhesion of cells to the extracorporeal device. The activation of inflammation, coagulation, and fibrinolysis was significantly reduced by the use of CHS. Both a reduced and an increased dose of systemic heparin in combination with the heparin-coated surface resulted in more activation of inflammation and coagulation.

Photoelectron spectroscopy studies of the molecular structure of the CHS demonstrated that a single layer of the heparin surface, equivalent to what was used in the in vivo studies, did not completely cover the substrate surface. Additional layer of immobilized heparin has resulted in a complete coverage. We examined the biological effects, i.e. activation of inflammation and coagulation, by CHS in one and two layers in an in vitro-study. The data from this study clearly demonstrated that a uniform surface coating of the CHS results in only minor activation of coagulation, inflammation and cell activation.

Monocytes do not normally express tissue factor (TF), initiator of the coagulation in vivo, but can be induced upon adhesion to artificial surfaces. TF is receptor for coagulation factor VIIa (FVIIa) and binding subsequently leads to formation of thrombin. Other biological effects beyond coagulation, as inflammation and angiogenesis, has recently been associated with the formation of TF·FVIIa. The TF∙FVIIa signal transduction induced an increased sensitivity to PDGF-BB-stimulated migration and an increased production of IL-8 and TNF-α in monocytes. These could be important mechanisms for continued recruitment of cells to sites of inflammation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 65 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1299
Medicine, monocytes, tissue factor, heparin-coated surfaces, coagulation, inflammation, thrombin, cytokines, cardiopulmonary bypass, biocompatibility, migration, chemotaxis, Medicin
National Category
Dermatology and Venereal Diseases
urn:nbn:se:uu:diva-3740 (URN)91-554-5779-7 (ISBN)
Public defence
2003-11-21, Robergsalen, ingång 40, Akademiska sjukhuset, Uppsala, 13:15
Available from: 2003-10-30 Created: 2003-10-30Bibliographically approved

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