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An assay to monitor in vitro generation of non-proteolytically activated C3 in human plasma
Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
Uppsala University Hospital.
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nyckelord [en]
C3, chaotropic agents, hepatic encephalopathy, iC3, nucleophilic agents, surface interaction
Nationell ämneskategori
Immunologi
Forskningsämne
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
URN: urn:nbn:se:lnu:diva-47388OAI: oai:DiVA.org:lnu-47388DiVA, id: diva2:873559
Forskningsfinansiär
Carl Tryggers stiftelse för vetenskaplig forskning VetenskapsrådetEU, FP7, Sjunde ramprogrammetTillgänglig från: 2015-11-24 Skapad: 2015-11-24 Senast uppdaterad: 2016-11-10Bibliografiskt granskad
Ingår i avhandling
1. Interaction between biomaterials and innate immunity with clinical implications
Öppna denna publikation i ny flik eller fönster >>Interaction between biomaterials and innate immunity with clinical implications
2015 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Today there is an increasing clinical demand and expectation of patients for biomaterials, which underscores the importance of discovering the correlations between biomaterials and biological systems, especially blood. When an artificial material makes contact with blood, the first event is a rapid adsorption of plasma protein on the material surface, on top of which the innate immune system is triggered, with potentially detrimental consequences. The work presented in this thesis, reported in four papers, was designed to investigate complications associated with (a) biomaterial-induced immune systems, including activation mechanisms and crosstalk between cascades on the biomaterial surface, and with (b) clinical investigations.

In Paper I and Paper II, a series of studies led to the development of a direct prediction of the subsequent biological events based on the pattern of initially bound proteins. A reciprocal relationship was demonstrated between activation of the contact system and the complement system when they were induced on artificial material surfaces. Based on these studies, a robust and simple method for biocompatibility testing was proposed and validated, yielding high specificity and sensitivity when compared to today’s gold standard. Paper III investigated biomaterial-induced activation of complement and leukocytes in dialysis treatment-related conditions. The results suggested that citrate is more biocompatible than the conventionally used acetate. This reduction in activation could be further enhanced with higher citrate concentrations, suggesting that dialysis fluid containing citrate is a promising alternative to acetate dialysis fluid. Paper IV investigated complement initiation mechanisms with clinical implications. An experimental system was set up to revisit the initiation of the complement alternative pathway, and correlations were found between chaotropic or nucleophilic agents and iC3 generation under physiologically relevant conditions. A clinical study of hepatic encephalopathy patients indicated a direct correlation between elevated plasma ammonia and iC3 formation, as well as with complement activation in vivo

Taken together, these studies have provided a model for a robust biomaterial test and have investigated biomaterial-induced complications in the fluid phase in clinically related conditions; furthermore, the basic mechanisms of complement activation have been dissected in relation to disease symptoms.

Keywords: Complement system, contact system, blood, biomaterials, biocompatibility, in vitro screening, iC3, dialysis

Ort, förlag, år, upplaga, sidor
Växjö: Linnaeus University Press, 2015
Serie
Linnaeus University Dissertations ; 236/2015
Nyckelord
Complement system, contact system, blood, biomaterials, biocompatibility, in vitro screening, iC3, dialysis
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
urn:nbn:se:lnu:diva-47391 (URN)978-91-87925-87-0 (ISBN)
Disputation
2015-12-18, N2007, Smålandsgatan 24, Kalmar, 09:30 (Engelska)
Opponent
Handledare
Tillgänglig från: 2015-11-26 Skapad: 2015-11-24 Senast uppdaterad: 2015-11-26Bibliografiskt granskad

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Huang, ShanSandholm, KerstinJonsson, NinaNilsson Ekdahl, Kristina

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Huang, ShanSandholm, KerstinJonsson, NinaNilsson Ekdahl, Kristina
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