• Alginate microbeads are complement compatible, in contrast to polycation containing microcapsules, as revealed in a human whole blood model 

      Rokstad, Anne Mari; Brekke, Ole Lars; Steinkjer, Bjørg; Ryan, Liv; Kolláriková, Gabriela; Strand, Berit Løkensgard; Skjåk-Bræk, Gudmund; Lacík, Igor; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)
      Alginate microbeads and microcapsules are presently under evaluation for future cell-based therapy. Defining their inflammatory properties with regard to humans is therefore essential. A lepirudine-based human whole blood model was used as an inflammation predictor by measuring complement and leukocyte stimulation. Alginate microbeads were complement-compatible since they did not activate complement ...
    • Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation 

      Ørning, Mathias Pontus; Hoem, Kine Samseth; Coron, Abba Elizabeth; Skjåk-Bræk, Gudmund; Mollnes, Tom Eirik; Brekke, Ole Lars; Espevik, Terje; Rokstad, Anne Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-03-16)
      The inflammatory potential of 12 types of alginate-based microspheres was assessed in a human whole blood model. The inflammatory potential could be categorized from low to high based on the four main alginate microsphere types; alginate microbeads, liquefied core poly-l-ornithine (PLO)-containing microcapsules, liquefied core poly-l-lysine (PLL)-containing microcapsules, and solid core PLL-containing ...
    • Application of the C3 inhibitor compstatin in a human whole blood model designed for complement research – 20 years of experience and future perspectives 

      Mollnes, Tom Eirik; Storm, Benjamin; Brekke, Ole Lars; Nilsson, Per H.; Lambris, John D. (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-05-13)
      The complex molecular and cellular biological systems that maintain host homeostasis undergo continuous crosstalk. Complement, a component of innate immunity, is one such system. Initially regarded as a system to protect the host from infection, complement has more recently been shown to have numerous other functions, including involvement in embryonic development, tissue modeling, and repair. ...
    • Association between brain-derived neurotropic factor (BDNF), high-sensitivity C-reactive protein (hs-CRP) and psychiatric symptoms in medicated and unmedicated patients 

      Soløy-Nilsen, Hedda; Nygård-Odeh, Kristin; Kristiansen, Magnhild Gangsøy; Brekke, Ole Lars; Mollnes, Tom Eirik; Reitan, Solveig Merete Klæbo; Øiesvold, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-02-03)
      Background - There is evidence that brain-derived neurotropic factor (BDNF) plays a protective role in the brain. Peripheral levels of BDNF correlate with its concentration in the brain. Previous studies have revealed lower serum BDNF levels in patients with mental illnesses. In most studies serum BDNF correlates negatively with psychiatric disorders and disease severity. Most studies in this field ...
    • Blood Transcriptome Analysis of Septic Patients Reveals a Long Non-Coding Alu-RNA in the Complement C5a Receptor 1 Gene 

      Emblem, Åse; Knutsen, Erik; Jørgensen, Tor Erik; Fure, Hilde; Johansen, Steinar Daae; Brekke, Ole Lars; Mollnes, Tom Eirik; Karlsen, Bård Ove (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-03-29)
      Many severe inflammation conditions are complement-dependent with the complement component C5a-C5aR1 axis as an important driver. At the RNA level, the blood transcriptome undergoes programmed expression of coding and long non-coding RNAs to combat invading microorganisms. Understanding the expression of long non-coding RNAs containing Alu elements in inflammation is important for reconstructing ...
    • Blood Transcriptome Analysis of Septic Patients Reveals a Long Non-Coding Alu-RNA in the Complement C5a Receptor 1 Gene 

      Emblem, Åse; Knutsen, Erik; Jørgensen, Tor Erik; Fure, Hilde; Johansen, Steinar Daae; Brekke, Ole Lars; Mollnes, Tom Eirik; Karlsen, Bård Ove (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-03-29)
      Many severe inflammation conditions are complement-dependent with the complement component C5a-C5aR1 axis as an important driver. At the RNA level, the blood transcriptome undergoes programmed expression of coding and long non-coding RNAs to combat invading microorganisms. Understanding the expression of long non-coding RNAs containing Alu elements in inflammation is important for reconstructing ...
    • 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 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 ...
    • 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 ...
    • 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 ...
    • Effect of the anticoagulant, storage time and temperature of blood samples on the concentrations of 27 multiplex assayed cytokines – Consequences for defining reference values in healthy humans 

      Hennø, Linda Torrissen; Storjord, Elin; Christiansen, Dorte; Bergseth, Grete; Ludviksen, Judith K; Fure, Hilde; Barene, Svein; Nielsen, Erik Waage; Mollnes, Tom Eirik; Brekke, Ole Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-06-06)
      Cytokines are potentially useful biomarkers of sepsis and other inflammatory conditions. Many cytokines can be released by leukocytes and platelets after sampling. The sampling and processing techniques are consequently critically important to measure the <i>in vivo</i> levels. We therefore examined the effects of four different anticoagulants, EDTA, citrate, lepirudin, heparin compared to serum, ...
    • Establishing IMMULITE® 2000 cut-off values for serum allergen-specific immunoglobulin and exploring their relationship to exhaled nitric oxide 

      Evjenth, Bjørg; Hansen, Tonje Elisabeth; Brekke, Ole Lars; Holt, Jan (Journal article; Tidsskriftartikkel; Peer reviewed, 2014-03-31)
      Aim: Paediatric cut-off values for serum allergen-specific IgE (sIgE) using the Siemens IMMULITE 2000 system to diagnose allergic rhinoconjunctivitis have not been established. We aimed to determine cut-off levels for sIgE for 10 common inhalant allergens and to study the relationship between sIgE, total IgE and fractional exhaled nitric oxide (FENO). <br>Methods: We enrolled 243 schoolchildren, ...
    • 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 ...
    • A Novel Porcine Model of Ischemia-Reperfusion Injury After Cross-Clamping the Thoracic Aorta Revealed Substantial Cardiopulmonary, Thromboinflammatory and Biochemical Changes Without Effect of C1-Inhibitor Treatment 

      Nielsen, Erik Waage; Miller, Yoav; Brekke, Ole Lars; Grond, Joost; Duong, Anh Hoang; Fure, Hilde; Ludviksen, Judith K; Pettersen, Kristin; Reubsaet, Leon; Solberg, Rigmor; Johansen, Harald Thidemann; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-01)
      Ischemic injury worsens upon return of blood and innate immunity including the complement system play a central role in ischemia-reperfusion injury (IRI) as in thoracic aortic surgery. Complement component1 inhibitor (C1-INH) has been shown to reduce IRI and is a broad-acting plasma cascade inhibitor. We established a new porcine model of IRI by cross-clamping the thoracic aorta and evaluated the ...