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dc.contributor.authorLandsem, Anne
dc.contributor.authorFure, Hilde
dc.contributor.authorLudviksen, Judith K
dc.contributor.authorChristiansen, Dorte
dc.contributor.authorLau, Corinna
dc.contributor.authorMathisen, Monica Dammen
dc.contributor.authorBergseth, Grete
dc.contributor.authorNymo, Stig Haugset
dc.contributor.authorLappegård, Knut Tore
dc.contributor.authorWoodruff, T. M.
dc.contributor.authorEspevik, Terje
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorBrekke, Ole-Lars
dc.date.accessioned2019-02-22T13:56:32Z
dc.date.available2019-02-22T13:56:32Z
dc.date.issued2018-12-19
dc.description.abstractThere is a close cross‐talk between complement, Toll‐like receptors (TLRs) and coagulation. The role of the central complement component 5 (C5) in physiological and pathophysiological hemostasis has not, however, been fully elucidated. This study examined the effects of C5 in normal hemostasis and in <i>Escherichia coli</i>‐induced coagulation and tissue factor (TF) up‐regulation. Fresh whole blood obtained from six healthy donors and one C5‐deficient individual (C5D) was anti‐coagulated with the thrombin inhibitor lepirudin. Blood was incubated with or without <i>E. coli</i> in the presence of the C5 inhibitor eculizumab, a blocking anti‐CD14 monoclonal antibody (anti‐CD14) or the TLR‐4 inhibitor eritoran. C5D blood was reconstituted with purified human C5. TF mRNA was measured by quantitative polymerase chain reaction (qPCR) and monocyte TF and CD11b surface expression by flow cytometry. Prothrombin fragment 1+2 (PTF1·2) in plasma and microparticles exposing TF (TF‐MP) was measured by enzyme‐linked immunosorbent assay (ELISA). Coagulation kinetics were analyzed by rotational thromboelastometry and platelet function by PFA‐200. Normal blood with eculizumab as well as C5D blood with or without reconstitution with C5 displayed completely normal biochemical hemostatic patterns. In contrast, <i>E. coli</i>‐induced TF mRNA and TF‐MP were significantly reduced by C5 inhibition. C5 inhibition combined with anti‐CD14 or eritoran completely inhibited the <i>E. coli</i>‐induced monocyte TF, TF‐MP and plasma PTF1·2. Addition of C5a alone did not induce TF expression on monocytes. In conclusion, C5 showed no impact on physiological hemostasis, but substantially contributed to <i>E. coli</i>‐induced procoagulant events, which were abolished by the combined inhibition of C5 and CD14 or TLR‐4.en_US
dc.description.sponsorshipNordland Hospital Trust The Norwegian Council on Cardiovascular Disease The Northern Norway Regional Health Authority The Southern and Eastern Norway Regional Health Authority The Odd Fellow Foundationen_US
dc.descriptionSource at <a href=https://doi.org/10.1111/cei.13240> https://doi.org/10.1111/cei.13240</a>.en_US
dc.identifier.citationLandsem, A., Fure, H., Ludviksen, J.K., Christiansen, D., Lau, C., Mathisen, M.T., ... Brekke, O. (2018). Complement component 5 does not interfere with physiological hemostasis but is essential for Escherichia coli-induced coagulation accompanied by Toll-like receptor 4. <i>Clinical and Experimental Immunology, 196</i>(1), 97-110. https://doi.org/10.1111/cei.13240en_US
dc.identifier.cristinIDFRIDAID 1674386
dc.identifier.doi10.1111/cei.13240
dc.identifier.issn0009-9104
dc.identifier.issn1365-2249
dc.identifier.urihttps://hdl.handle.net/10037/14751
dc.language.isoengen_US
dc.publisherWileyen_US
dc.relation.ispartofLandsem, A. (2019). The role of complement and Toll-like receptors in thromboinflammation. (Doctoral thesis). <a href=https://hdl.handle.net/10037/15243>https://hdl.handle.net/10037/15243. </a>
dc.relation.journalClinical and Experimental Immunology
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/SFF/223255/Norway/Centre of Molecular Inflammation Research/CEMIR/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7-HEALTH/602699/EU/Disarming the intravascular innate immune response to improve treatment modalities for chronic kidney disease/DIREKT/en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical immunology: 716en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk immunologi: 716en_US
dc.subjectCD14en_US
dc.subjectcomplementen_US
dc.subjectC5en_US
dc.subjectEscherichia colien_US
dc.subjecttissue factoren_US
dc.subjectToll‐like receptor 4en_US
dc.titleComplement component 5 does not interfere with physiological hemostasis but is essential for Escherichia coli-induced coagulation accompanied by Toll-like receptor 4en_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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