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The creation of an antithrombotic surface by apyrase immobilization
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.ORCID iD: 0000-0002-7192-5794
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
Div. Clinical Immunology, Rudbeck Laboratory, University Hospital, Uppsala.
Department of Clinical Chemistry, Laboratory Medicine, University Hospital, Linköping.
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2010 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 31, no 16, p. 4484-4491Article in journal (Refereed) Published
Abstract [en]

Blood incompatibility reactions caused by surfaces often involve platelet activation and subsequent platelet-initiated activation of the coagulation and complement cascades. The goal of this study was to immobilize apyrase on a biomaterial surface in order to develop an enzymatically active surface that would have the capacity to inhibit platelet activation by degrading ADP. We were able to immobilize apyrase on a polystyrene surface with preservation of the enzymatic activity. We then analyzed the hemocompatibility of the apyrase surface and of control surfaces by incubation with platelet-rich plasma (PRP) or whole blood. Monitoring of markers of platelet, coagulation, and complement activation and staining of the surfaces revealed decreased levels of platelet and coagulation activation parameters on the apyrase surface. The formation of antithrombin-thrombin and antithrombin-factor XIa complexes and the extent of platelet consumption were significantly lower on the apyrase surface than on any of the control surfaces. No significant differences were seen in complement activation (C3a levels). Staining of the apyrase surface revealed low platelet adherence and no formation of granulocyte platelet complexes. These results demonstrate that it is possible to create an antithrombotic surface targeting the ADP amplification of platelet activation by immobilizing apyrase.

Place, publisher, year, edition, pages
2010. Vol. 31, no 16, p. 4484-4491
Keyword [en]
Blood compatibiliy; Apyrase; Platelet; Platelet regulation; Adenosine diphosphate
National Category
Immunology in the medical area
Research subject
Biomedical Sciences, Immunology; Natural Science, Biomedical Sciences
Identifiers
URN: urn:nbn:se:lnu:diva-2176DOI: 10.1016/j.biomaterials.2010.02.036Scopus ID: 2-s2.0-77950061949OAI: oai:DiVA.org:lnu-2176DiVA, id: diva2:309226
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2018-01-12Bibliographically approved
In thesis
1. Interactions between platelets and complement with implications for the regulation at surfaces
Open this publication in new window or tab >>Interactions between platelets and complement with implications for the regulation at surfaces
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Disturbances of host integrity have the potential to evoke activation of innate immunologic and hemostatic protection mechanisms in blood. Irrespective of whether the activating stimulus is typically immunogenic or thrombotic, it will generally affect both the complement system and platelets to a certain degree. The theme of this thesis is complement and platelet activity, which is intersected in all five included papers. The initial aim was to study the responses and mechanisms of the complement cascade in relation to platelet activation. The secondary aim was to use an applied approach to regulate platelets and complement on model biomaterial and cell surfaces.   

Complement activation was found in the fluid phase in response to platelet activation in whole blood. The mechanism was traced to platelet release of stored chondroitin sulfate-A (CS-A) and classical pathway activation via C1q. C3 was detected at the platelet surface, though its binding was independent of complement activation. The inhibitors factor H and C4-binding protein (C4BP) were detected on activated platelets, and their binding was partly dependent on surface-exposed CS-A. Collectively, these results showed that platelet activation induces inflammatory complement activation in the fluid phase. CS-A was shown to be a central molecule in the complement-modulatory functions of platelets by its interaction with C1q, C4BP, and factor H.

Platelet activation and surface adherence were successfully attenuated by conjugating an ADP-degrading apyrase on a model biomaterial. Only minor complement regulation was seen, and was therefore targeted specifically on surfaces and cells by co-immobilizing a factor H-binding peptide together with the apyrase. This combined approach led to a synchronized inhibition of both platelet and complement activation at the interface of biomaterials/xenogeneic cells and blood.

In conclusion, here presents a novel crosstalk-mechanism for activation of complement when triggering platelets, which highlights the importance of regulating both complement and platelets to lower inflammatory events. In addition, a strategy to enhance the biocompatibility of biomaterials and cells by simultaneously targeting ADP-dependent platelet activation and the alternative complement C3-convertase is proposed.

Place, publisher, year, edition, pages
Växjö, Kalmar: Linnaeus University Press, 2012. p. 87
Series
Linnaeus University Dissertations ; 83/2012
Keyword
complement system (activation, regulation), platelets (activation, regulation), biomaterials, biocompatibility, chondroitin sulfate-A, apyrase, C1q, C3, factor H, C4BP, ADP
National Category
Immunology Biomaterials Science Biochemistry and Molecular Biology Cell and Molecular Biology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-18321 (URN)978-91-86983-46-8 (ISBN)
Public defence
2012-05-11, N2007, Smålandsgatan 26, Kalmar, 09:30 (English)
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Available from: 2012-04-16 Created: 2012-04-13 Last updated: 2018-01-12Bibliographically approved

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Nilsson, Per H.Engberg, Anna E.Nilsson Ekdahl, Kristina

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