Blar i forfatter "Lau, Corinna"

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    • 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, ...

    • CD14 and complement crosstalk and largely mediate the transcriptional response to Escherichia coli in human whole blood as revealed by DNA microarray 

      Lau, Corinna; Nygård, Ståle; Fure, Hilde; Olstad, Ole Kristoffer; Holden, Marit; Lappegård, Knut Tore; Brekke, Ole Lars; Espevik, Terje; Hovig, Johannes Eivind; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-02-23)
      Systemic inflammation like in sepsis is still lacking specific diagnostic markers and effective therapeutics. The first line of defense against intruding pathogens and endogenous damage signals is pattern recognition by e.g., complement and Toll-like receptors (TLR). Combined inhibition of a key complement component (C3 and C5) and TLR-co-receptor CD14 has been shown to attenuate certain systemic ...

    • Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome 

      Thomas, Anub Mathew; Schjalm, Camilla; Nilsson, Per; Lindenskov, Paal Helge H.; Rørtveit, Runa; Solberg, Rønnaug; Saugstad, Ola Didrik; Berglund, Magnus M.; Strömberg, Patrik; Lau, Corinna; Espevik, Terje; Jansen, Johan Høgset; Castellheim, Albert; Mollnes, Tom Eirik; Barratt-Due, Andreas (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-27)
      <p><i>Background</i>: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors.</p> <p><i>Objectives</i>: To ...

    • Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis 

      Hellerud, Bernt C; Orrem, Hilde L.; Dybwik, Knut Gustav; Pischke, Søren Erik; Barratt-Due, Andreas; Castellheim, Albert; Fure, Hilde; Bergseth, Grete; Christiansen, Dorte; Nunn, Miles A.; Espevik, Terje; Lau, Corinna; Brandtzæg, Petter; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-02-27)
      Background<br> Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key molecules of innate immunity, complement component C5, and co-receptor CD14 in the Toll-like receptor system, on the inflammatory response in meningococcal sepsis.<p> Methods ...

    • 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 ...

    • Combined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsis 

      Skjeflo, Espen Waage; Sagatun, Caroline; Dybwik, Knut; Aam, Sturla; Urving, Sven Haakon; Nunn, Miles A.; Fure, Hilde; Lau, Corinna; Brekke, Ole Lars; Huber-Lang, Markus; Barratt-Due, Andreas; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-11-27)
      Introduction: Sepsis is an exaggerated and dysfunctional immune response to infection. Activation of innate immunity recognition systems including complement and the Toll-like receptor family initiate this disproportionate inflammatory response. The aim of this study was to explore the effect of combined inhibition of the complement component C5 and the Toll-like receptor co-factor CD14 on survival, ...

    • 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 ...

    • Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn 

      Hallstensen, Randi; Bergseth, Grete; Foss, Stian; Jæger, Steinar; Gedde-Dahl, Thobias; Holt, jan; Christiansen, Dorte; Lau, Corinna; Brekke, Ole Lars; Armstrong, Elina; Stefanovic, Vedran; Andersen, Jan Terje; Sandlie, Inger; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-11-13)
      Eculizumab is a humanized IgG2/4 chimeric anti-complement C5 antibody used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome. The aim of this study was to evaluate whether or not the complement activity in newborns from pregnant women who receive eculizumab is impaired. A novel eculizumab-C5 complex (E-C5) specific assay was developed and ...

    • Gene expression profiling of Gram-negative bacteria-induced inflammation in human whole blood: The role of complement and CD14-mediated innate immune response 

      Lau, Corinna; Olstad, Ole Kristoffer; Holden, Marit; Nygård, Ståle; Fure, Hilde; Lappegård, Knut Tore; Brekke, Ole Lars; Espevik, Terje; Hovig, Johannes Eivind; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-05-30)
      Non-sterile pathogen-induced sepsis and sterile inflammation like in trauma or ischemia–reperfusion injury may both coincide with the life threatening systemic inflammatory response syndrome and multi-organ failure. Consequently, there is an urgent need for specific biomarkers in order to distinguish sepsis from sterile conditions. The overall aim of this study was to uncover putative sepsis ...

    • NHDL, a recombinant VL/VH hybrid antibody control for IgG2/4 antibodies. 

      Lau, Corinna; McAdam, MB; Bergseth, G; Grevys, Algirdas; Bruun, JA; Ludviksen, Judith K; Fure, Hilde; Espevik, Terje; Moen, A; Andersen, Jan Terje; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-11-27)
      The mechanism of action of recombinant IgG2/4 antibodies involves blocking of their target without the induction of effector functions. Examples are eculizumab (Soliris®), which is used clinically to block complement factor C5, as well as anti-human CD14 (r18D11) and anti-porcine CD14 (rMIL2) produced in our laboratory. So far, no proper IgG2/4 control antibody has been available for controlled ...

    • Thrombin Differentially Modulates the Acute Inflammatory Response to Escherichia coli and Staphylococcus aureus in Human Whole Blood 

      Johnson, Christina; Quach, Huy Quang; Lau, Corinna; Ekholt, Karin; Espevik, Terje; Woodruff, Trent M.; Pischke, Soeren; Mollnes, Tom Eirik; Nilsson, Per (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-06-15)
      Thrombin plays a central role in thromboinflammatory responses, but its activity is blocked in the common ex vivo human whole blood models, making an ex vivo study of thrombin effects on thromboinflammatory responses unfeasible. In this study, we exploited the anticoagulant peptide Gly-Pro-Arg-Pro (GPRP) that blocks fibrin polymerization to study the effects of thrombin on acute inflammation in ...