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Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood
Linnaeus Univ, Ctr Biomat Chem, Kalmar, Sweden.;Univ & Reg Labs Reg, Dept Clin Chem, Skane, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2016 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 77, 111-119 p.Article in journal (Refereed) Published
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Abstract [en]

Background: Inappropriate and uncontrolled activation of the cascade systems in the blood is a driving force in adverse inflammatory and thrombotic reactions elicited by biomaterials, but limited data are available on the activation of the contact system by polymers and the present study was undertaken to investigate these mechanisms in established models. Methods: Polymer particles were incubated in (1) EDTA-plasma (10 mM) to monitor the adsorption of 20 selected proteins; (2) lepirudin-anticoagulated plasma to evaluate contact system activation, monitored by the formation of complexes between the generated proteases factor[F]XIIa, FXIa and kallikrein and the serpins C1-inhibitor [C1INH] and antithrombin [AT]; (3) lepirudin-anticoagulated whole blood to determine cytokine release. Results: Strong negative correlations were found between 10 cytokines and the ratio of deposited FXII/C1INH, generated FXIIa-C1INH complexes, and kallikrein-C1INH complexes. Formation of FXIIa-C1INH complexes correlated negatively with the amount of C3a and positively with deposited IgG. Conclusions: A reciprocal relationship was found between activation of the contact system and the complement system induced by the polymers studied here. The ratios of FXII/C1INH or C4/C4BP, adsorbed from EDTA-plasma are useful surrogate markers for cytokine release and inflammatory response to materials intended for blood contact.

Place, publisher, year, edition, pages
2016. Vol. 77, 111-119 p.
Keyword [en]
Biomaterials, Complement system, Contact system, FXII, In vitro screening
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-274422DOI: 10.1016/j.biomaterials.2015.10.067ISI: 000367118200010OAI: oai:DiVA.org:uu-274422DiVA: diva2:896548
Funder
Swedish Research CouncilEU, European Research Council, 602699Carl Tryggers foundation
Available from: 2016-01-21 Created: 2016-01-21 Last updated: 2017-11-30Bibliographically approved

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Nicholls, Ian A.Fromell, KarinNilsson, BoEkdahl, Kristina N.

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Department of Immunology, Genetics and PathologyDepartment of Chemistry - BMCClinical Immunology
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Biomaterials
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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