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Inhibition of complement activation on a model biomaterial surface by streptococcal M protein-derived peptides
University of Kalmar, School of Pure and Applied Natural Sciences.
University of Kalmar, School of Pure and Applied Natural Sciences.
University of Kalmar, School of Pure and Applied Natural Sciences.
Lund University.ORCID iD: 0000-0002-1075-4346
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2009 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, no 13, p. 2653-2659Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to evaluate a new approach to inhibit complement activation triggered by biomaterial surfaces in contact with blood. In order to inhibit complement activation initiated by the classical pathway (CP), we used streptococcal M protein-derived peptides that specifically bind human C4BP, an inhibitor of the CP. The peptides were used to coat polystyrene microtiter wells which served as a model biomaterial. The ability of coated peptides to bind C4BP and to attenuate complement activation via the CP (monitored as generation of fluid-phase C3a and binding of fragments of C3 and C4 to the surface) was investigated using diluted normal human serum, where complement activation by the AP is minimal, as well as serum from a patient lacking alternative pathway activation. Complement activation (all parameters) was significantly decreased in serum incubated in well surfaces coated with peptides. Total inhibition of complement activation was obtained at peptide coating concentrations as low as 1-5 mu g/mL. Successful use of Streptococcus-derived peptides shows that it is feasible to control complement activation at a model biomaterial surface by capturing autologous complement regulatory molecules from plasma. (C) 2009 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2009. Vol. 30, no 13, p. 2653-2659
Keyword [en]
Blood compatibility, Complement, C4b-binding protein (C4BP), In vitro test, Regulator of complement activation (RCA), Streptococcal M proteins
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
URN: urn:nbn:se:lnu:diva-73088DOI: 10.1016/j.biomaterials.2009.01.001ISI: 000264691200026PubMedID: 19171378OAI: oai:DiVA.org:lnu-73088DiVA, id: diva2:1199048
Available from: 2018-04-19 Created: 2018-04-19 Last updated: 2018-04-19Bibliographically approved
In thesis
1. Biomaterials and Hemocompatibility
Open this publication in new window or tab >>Biomaterials and Hemocompatibility
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biomaterials are commonly used in the medical clinic today; however, artificial materials can activate the cascade systems in the blood (complement-, coagulation-, contact- and fibrinolytic systems) as well as the platelets to various degrees. When an artificial surface comes in contact with blood, plasma proteins will be adsorbed to the surface within seconds. The composition of the layer of proteins differs between materials and is crucial for the hemocompatibility of the material.

This thesis includes five projects.

In Paper I the anticoagulants heparin and the thrombin inhibitor hirudin were evaluated in a whole blood model. Hirudin was found to be superior to low dose heparin since it did not affect the activation of the complement system nor the leukocytes. The most interesting observation was that expression of TF was seen on surface-attached monocytes in hirudin- treated blood but not heparin blood.

In Paper II peptides from the streptococcal M-protein, which has affinity for the human complement inhibitor C4BP, were attached to a polymeric surface. When being exposed to blood the endogenous complement regulator was enriched at the surface of the material, via the M-peptides. With this new approach we created a self-regulatory surface, showing significant lowered material-induced complement activation.

In Paper III apyrase, an enzyme which hydrolyzes nucleoside ATP and ADP, was immobilized on a polymer surface. Lower platelet activation and platelet-induced coagulation activation was seen for the apyrase-coated surface compared to control surfaces after exposure to whole human blood, due to the enzymes capability to degrade ADP released from activated platelets.

In Paper IV and V we synthesized an array of polymeric materials which were characterized regarding physical-chemical properties, adsorption of plasma proteins, and hemocompatibility. The polymers showed widely heterogeneous protein adsorption. Furthermore, when the polymers were exposed to whole blood, two of the materials showed superior hemocompatibility (monitored as complement- and coagulation activation), compared to the reference poly(vinyl chloride).

Place, publisher, year, edition, pages
Kalmar, Växjö: Linnaeus University Press, 2010. p. 167
Series
Linnaeus University Dissertations ; 2/2010
Keyword
Complement, Coagulation, Whole blood, Biomaterials, Polymers and Hemocompatibility
National Category
Immunology in the medical area
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-5437 (URN)978-91-86491-01-7 (ISBN)
Public defence
2010-01-29, N2007, Smålandsgatan 26, Kalmar, 09:30 (English)
Opponent
Supervisors
Available from: 2010-04-30 Created: 2010-04-29 Last updated: 2018-04-19Bibliographically approved

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Engberg, Anna E.Sandholm, KerstinBexborn, FredrikNilsson Ekdahl, Kristina

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