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dc.contributor.authorStorm, Benjamin
dc.contributor.authorChristiansen, Dorte
dc.contributor.authorFure, Hilde
dc.contributor.authorLudviksen, Judith K
dc.contributor.authorLau, Corinna
dc.contributor.authorLambris, John D.
dc.contributor.authorWoodruff, Trent M.
dc.contributor.authorBrekke, Ole-Lars
dc.contributor.authorBraaten, Tonje Bjørndal
dc.contributor.authorNielsen, Erik Waage
dc.contributor.authorMollnes, Tom Eirik
dc.date.accessioned2022-02-02T11:48:37Z
dc.date.available2022-02-02T11:48:37Z
dc.date.issued2021-11-03
dc.description.abstractVenous air embolism, which may complicate medical and surgical procedures, activates complement and triggers thromboinflammation. In lepirudin-anticoagulated human whole blood, we examined the effect of air bubbles on complement and its role in thromboinflammation. Whole blood from 16 donors was incubated with air bubbles without or with inhibitors of C3, C5, C5aR1, or CD14. Complement activation, hemostasis, and cytokine release were measured using ELISA and quantitative PCR. Compared with no air, incubating blood with air bubbles increased, on average, C3a 6.5-fold, C3bc 6-fold, C3bBbP 3.7-fold, C5a 4.6- fold, terminal complement complex sC5b9 3.6-fold, prothrombin fragments 1+2 (PTF1+2) 25-fold, tissue factor mRNA (TF-mRNA) 26- fold, microparticle tissue factor 6.1-fold, b-thromboglobulin 26-fold (all p < 0.05), and 25 cytokines 11-fold (range, 1.5 78-fold; all p < 0.0001). C3 inhibition attenuated complement and reduced PTF1+2 2-fold, TF-mRNA 5.4-fold, microparticle tissue factor 2-fold, and the 25 cytokines 2.7-fold (range, 1.4 4.9-fold; all p < 0.05). C5 inhibition reduced PTF1+2 2-fold and TF-mRNA 12-fold (all p < 0.05). C5 or CD14 inhibition alone reduced three cytokines, including IL-1b (p 5 0.02 and p 5 0.03). Combined C3 and CD14 inhibition reduced all cytokines 3.9-fold (range, 1.3 9.5-fold; p < 0.003) and was most pronounced for IL-1b (3.2- versus 6.4-fold), IL-6 (2.5- versus 9.3-fold), IL-8 (4.9- versus 8.6-fold), and IFN-g (5- versus 9.5-fold). Antifoam activated complement and was avoided. PTF1+2 was generated in whole blood but not in plasma. In summary, air bubbles activated complement and triggered a C3-driven thromboinflammation. C3 inhibition reduced all mediators, whereas C5 inhibition reduced only TF-mRNA. Combined C5 and CD14 inhibition reduced IL-1b release. These data have implications for future mechanistic studies and possible pharmacological interventions in patients with air embolism.en_US
dc.identifier.citationStorm BS, Christiansen D, Fure H, Ludviksen JK, Lau C, Lambris JD, Woodruff TM, Brekke O.L., Braaten T, Nielsen EW, Mollnes TE. Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood. Journal of Immunology. 2021;207(11):2828-2840en_US
dc.identifier.cristinIDFRIDAID 1977941
dc.identifier.doi10.4049/jimmunol.2100308
dc.identifier.issn0022-1767
dc.identifier.issn1550-6606
dc.identifier.urihttps://hdl.handle.net/10037/23902
dc.language.isoengen_US
dc.publisherAmerican Association of Immunologistsen_US
dc.relation.ispartofStorm, B. (2022). Venous Air Embolism and Complement-driven Thromboinflammation. In vitro human whole blood studies and in vivo porcine studies on the effect of air emboli on the complement system, cytokine network, and the hemostasis. (Doctoral thesis). <a href=https://hdl.handle.net/10037/25922>https://hdl.handle.net/10037/25922</a>.
dc.relation.journalJournal of Immunology
dc.relation.projectIDNorges forskningsråd: 223255en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/SFF/223255/Norway/Centre of Molecular Inflammation Research/CEMIR/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.titleAir Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blooden_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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