• Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood 

      Storm, Benjamin; Christiansen, Dorte; Fure, Hilde; Ludviksen, Judith K; Lau, Corinna; Lambris, John D.; Woodruff, Trent M.; Brekke, Ole-Lars; Braaten, Tonje Bjørndal; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-11-03)
      Venous 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, ...
    • Associations between complement pathways activity, mannose-binding lectin, and odds of unprovoked venous thromboembolism 

      Høiland, Ina Isabella; Liang, Robin Amanda; Hindberg, Kristian; Latysheva, Nadezhda; Brekke, Ole-Lars; Mollnes, Tom Eirik; Hansen, John-Bjarne (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-06-30)
      INTRODUCTION: Deep vein thrombosis (DVT) originates in the valvular sinuses of large veins in a local milieu characterized by stasis and severe hypoxia. This may induce complement- and coagulation activation, which potentially increases the risk of venous thromboembolism (VTE). The aim of the present study was to investigate whether the activity of the complement pathways, the level of mannose-binding ...
    • Cholesterol Crystals Induce coagulation Activation through Complement-Dependent Expression of Monocytic Tissue Factor 

      Gravastrand, Caroline S.; Steinkjer, Bjørg; Halvorsen, Bente; Landsem, Anne; Skjelland, Mona; Jacobsen, Eva Astrid; Woodruff, Trent M.; Lambris, John D.; Mollnes, Tom Eirik; Brekke, Ole-Lars; Espevik, Terje; Rokstad, Anne Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-03)
      Cholesterol crystals (CC) are strong activators of complement and could potentially be involved in thromboinflammation through complement-coagulation cross-talk. To explore the coagulation-inducing potential of CC, we performed studies in lepirudin-based human whole blood and plasma models. In addition, immunohistological examinations of brain thrombi and vulnerable plaque material from patients ...
    • Complement component 5 does not interfere with physiological hemostasis but is essential for Escherichia coli-induced coagulation accompanied by Toll-like receptor 4 

      Landsem, Anne; Fure, Hilde; Ludviksen, Judith K; Christiansen, Dorte; Lau, Corinna; Mathisen, Monica Dammen; Bergseth, Grete; Nymo, Stig Haugset; Lappegård, Knut Tore; Woodruff, T. M.; Espevik, Terje; Mollnes, Tom Eirik; Brekke, Ole-Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-12-19)
      There 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 ...
    • A conformational change of complement C5 is required for thrombin-mediated cleavage, revealed by a novel ex vivo human whole blood model preserving full thrombin activity 

      Nilsson, Per; Johnson, Christina; Quach, Huy Quang; Macpherson, Alex; Durrant, Oliver; Pischke, Soeren; Fure, Hilde; Landsem, Anne; Bergseth, Grete; Schjalm, Camilla; Haugaard-Kedström, Linda M.; Huber-Lang, Markus; van den Elsen, Jean; Brekke, Ole-Lars; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-09-15)
      Thrombin activation of C5 connects thrombosis to inflammation. Complement research in whole blood ex vivo necessitates anticoagulation, which potentially interferes with the inflammatory modulation by thrombin. We challenged the concept of thrombin as an activator of native C5 by analyzing complement activation and C5 cleavage in human whole blood anticoagulated with Gly-Pro-Arg-Pro (GPRP), a peptide ...
    • Granulocyte and monocyte CD11b expression during plasma separation is dependent on complement factor 5 (C5) – an ex vivo study with blood from a C5-deficient individual 

      Hardersen, Randolf Inge; Enebakk, Terje; Christiansen, Dorte; Bergseth, Grete; Brekke, Ole-Lars; Mollnes, Tom Eirik; Lappegård, Knut Tore; Hovland, Anders (Journal article; Tidsskriftartikkel, 2018)
      The aim of the study was to investigate the role of complement factor 5 (C5) in reactions elicited by plasma separation using blood from a C5‐deficient (C5D) individual, comparing it to C5‐deficient blood reconstituted with C5 (C5DR) and blood from healthy donors. Blood was circulated through an <i>ex vivo</i> plasma separation model. Leukocyte CD11b expression and leukocyte–platelet conjugates were ...
    • Key role of the number of complement receptor 1 on erythrocytes for binding of Escherichia coli to erythrocytes and for leukocyte phagocytosis and oxidative burst in human whole blood 

      Brekke, Ole-Lars; Christiansen, Dorte; Kisserli, Aymric; Fure, Hilde; Dahl, Jim André; Donvito, Béatrice; Reveil, Brigitte; Ludviksen, Judith K; Tabary, Thierry; Mollnes, Tom Eirik; Cohen, Jacques H.M. (Journal article; Tidsskriftartikkel, 2019-07-25)
      <i>Aim</i> - To study the role of complement receptor 1 (CR1) for binding of <i>Escherichia coli (E. coli)</i> to erythrocytes, for leukocyte phagocytosis, oxidative burst and complement activation in human whole blood from a CR1 deficient (CR1D) patient and healthy controls with low, medium and high CR1 numbers.<p> <p><i>Methods</i> - Alexa-labelled bacteria were used to quantify ...
    • Lifestyle factors including diet and biochemical biomarkers in acute intermittent porphyria: Results from a case-control study in northern Norway 

      Storjord, Elin; Dahl, Jim André; Landsem, Anne; Ludviksen, Judith K; Karlsen, Marlene; Karlsen, Bård Ove; Brekke, Ole-Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-12-10)
      <i>Background</i>: Lifestyle factors, including a low intake of carbohydrates, dieting, alcohol consumption, cigarette smoking and stress are some of the possible triggers of attacks in acute intermittent porphyria (AIP). The influence of lifestyle factors, including energy intake, diet and alcohol consumption on the biochemical disease activity in AIP and biochemical nutritional markers were ...
    • Staphylococcus aureus-induced complement activation promotes tissue factor-mediated coagulation 

      Skjeflo, Espen Waage; Christiansen, Dorte; Fure, Hilde; Ludviksen, Judith K; Woodruff, Trent M.; Espevik, Terje; Nielsen, Erik Waage; Brekke, Ole-Lars; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-13)
      <p><i>Background - </i>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. <p><i>Objectives - </i>To study the relative roles of complement, TLRs and TF in <i>Staphylococcus aureus</i>‐induced coagulation. <p><i>Methods - ...