Show simple item record

dc.contributor.authorSkjeflo, Espen Waage
dc.contributor.authorChristiansen, Dorte
dc.contributor.authorFure, Hilde
dc.contributor.authorLudviksen, Judith K
dc.contributor.authorWoodruff, Trent M.
dc.contributor.authorEspevik, Terje
dc.contributor.authorNielsen, Erik Waage
dc.contributor.authorBrekke, Ole-Lars
dc.contributor.authorMollnes, Tom Eirik
dc.identifier.citationJournal of Thrombosis and Haemostasis. 2018, 16 (5), 905-918.nb_NO
dc.description.abstractBackground There is extensive cross‐talk between the complement system, the Toll‐like receptors (TLRs), and hemostasis. Consumptive coagulopathy is a hallmark of sepsis, and is often mediated through increased tissue factor (TF) expression. Objectives To study the relative roles of complement, TLRs and TF in Staphylococcus aureus‐induced coagulation. Methods Lepirudin‐anticoagulated human whole blood was incubated with the three S. aureus strains Cowan, Wood, and Newman. C3 was inhibited with compstatin, C5 with eculizumab, C5a receptor 1 (C5aR1) and activated factor XII with peptide inhibitors, CD14, TLR2 and TF with neutralizing antibodies, and TLR4 with eritoran. Complement activation was measured by ELISA. Coagulation was measured according to prothrombin fragment 1 + 2 (PTF1 + 2) determined with ELISA, and TF mRNA, monocyte surface expression and functional activity were measured with quantitative PCR, flow cytometry, and ELISA, respectively. Results All three strains generated substantial and statistically significant amounts of C5a, terminal complement complex, PTF1 + 2, and TF mRNA, and showed substantial TF surface expression on monocytes and TF functional activity. Inhibition of C5 cleavage most efficiently and significantly inhibited all six markers in strains Cowan and Wood, and five markers in Newman. The effect of complement inhibition was shown to be completely dependent on C5aR1. The C5 blocking effect was equally potentiated when combined with blocking of CD14 or TLR2, but not TLR4. TF blocking significantly reduced PTF1 + 2 levels to baseline levels. Conclusions S. aureus‐induced coagulation in human whole blood was mainly attributable to C5a‐induced mRNA upregulation, monocyte TF expression, and plasma TF activity, thus underscoring complement as a key player in S. aureus‐induced coagulation.nb_NO
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.titleStaphylococcus aureus-induced complement activation promotes tissue factor-mediated coagulationnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalJournal of Thrombosis and Haemostasisnb_NO
dc.description.localcode© 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License.nb_NO
cristin.unitnameInstitutt for klinisk og molekylær medisin

Files in this item


This item appears in the following Collection(s)

Show simple item record

Navngivelse-Ikkekommersiell 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse-Ikkekommersiell 4.0 Internasjonal