• 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 ...
    • Combined inhibition of complement and CD14 attenuates bacteria-induced inflammation in human whole blood more efficiently than antagonizing the toll-like receptor 4-MD2 complex 

      Gustavsen, Alice; Nymo, Stig Haugset; Landsem, Anne; Christiansen, Dorte; Ryan, Liv; Husebye, Harald; Lau, Corinna; Pischke, Søren Erik; Lambris, John D.; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-03-14)
      <i>Background</i>: Single inhibition of the Toll-like receptor 4 (TLR4)–MD2 complex failed in treatment of sepsis. CD14 is a coreceptor for several TLRs, including TLR4 and TLR2. The aim of this study was to investigate the effect of single TLR4-MD2 inhibition by using eritoran, compared with the effect of CD14 inhibition alone and combined with the C3 complement inhibitor compstatin (Cp40), on the ...
    • Complement C3b contributes to Escherichia coli-induced platelet aggregation in human whole blood 

      Landsem, Anne; Emblem, Åse; Lau, Corinna; Christiansen, Dorte; Gerogianni, Alexandra; Karlsen, Bård Ove; Mollnes, Tom Eirik; Nilsson, Per; Brekke, Ole Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-12-14)
      We found that compstatin, which inhibits the cleavage of complement component C3 to its components C3a and C3b, reduced the E. coli-induced platelet aggregation by 42%-76% (p = 0.0417). This C3-dependent aggregation was not C3a-mediated as neither inhibition of C3a using a blocking antibody or a C3a receptor antagonist, nor the addition of purified C3a had any effects. In contrast, a C3b-blocking ...
    • 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 ...
    • Dental and Periodontal Health in Acute Intermittent Porphyria 

      Storjord, Elin; Airila-Månsson, Stella; Karlsen, Katarzyna; Madsen, Martin Ragnar Skjerve; Dahl, Jim André; Landsem, Anne; Fure, Hilde; Ludviksen, Judith K; Fjøse, Johannes Østrem; Dickey, Amy K.; Karlsen, Bård Ove; Nielsen, Erik Waage; Mollnes, Tom Eirik; Brekke, Ole Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-08-19)
      In the inherited metabolic disorder acute intermittent porphyria (AIP), high sugar intake prevents porphyric attacks due to the glucose effect and the following high insulin levels that may lower AIP disease activity. Insulin resistance is a known risk factor for periodontitis and sugar changes diabetogenic hormones and affects dental health. We hypothesized differences in homeostasis model ...
    • 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 ...
    • Phagocytosis of live and dead Escherichia coli and Staphylococcus aureus in human whole blood is markedly reduced by combined inhibition of C5aR1 and CD14 

      Skjeflo, Espen Waage; Christiansen, Dorte; Landsem, Anne; Stenvik, Jørgen; Woodruff, T. M.; Espevik, Terje; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-05-15)
      <i>Background</i> - Sepsis is a dysregulated host response to infection. The aim of this study was to investigate the effects of complement- and CD14 inhibition on phagocytosis of live and dead Gram-negative and Gram-positive bacteria in human whole blood.<p> <p><i>Methods</i> - Lepirudin-anticoagulated blood was incubated with live or dead <i>E. coli</i> or <i>S. aureus</i> at 37 °C for 120 min ...
    • The role of complement and Toll-like receptors in thromboinflammation 

      Landsem, Anne (Doctoral thesis; Doktorgradsavhandling, 2019-05-23)
      Sepsis fra bakterier er en alvorlig tilstand som årlig krever mange liv. Selv om immunsystemet og det hemostatiske system samarbeider for å bekjempe bakterieinfeksjoner, kan dette i noen tilfelle skyte over mål. Derfor har vi i denne studien undersøkt om bakterieindusert aktivering av koagulasjon og inflammasjon reduseres av en dobbelthemming av komplementsystemet og toll-like reseptorer (TLR). Det ...
    • Venous Air Embolism Activates Complement C3 Without Corresponding C5 Activation and Trigger Thromboinflammation in Pigs 

      Storm, Benjamin; Ludviksen, Judith K; Christiansen, Dorte; Fure, Hilde; Pettersen, Kristin; Landsem, Anne; Nilsen, Bent Aksel; Dybwik, Knut Gustav; Braaten, Tonje; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-03-15)
      Introduction: Air embolism may complicate invasive medical procedures. Bubbles trigger complement C3-mediated cytokine release, coagulation, and platelet activation in vitro in human whole blood. Since these findings have not been verified in vivo, we aimed to examine the effects of air embolism in pigs on thromboinflammation.<p> <p>Methods: Forty-five landrace pigs, average 17 kg (range 8.5-30), ...