• Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock 

      Orrem, Hilde L.; Nilsson, Per H.; Pischke, Søren Erik; Grindheim, Guro; Garred, Peter; Seljeflot, Ingebjørg; Husebye, Trygve; Aukrust, Pål; Yndestad, Arne; Andersen, Geir Ø.; Barratt-Due, Andreas; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-09)
      Aims: Heart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction. <br> <br> Methods and results: The LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary ...
    • Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population 

      Gaya de Costa, Mariana; Poppelaars, Felix; van Kooten, Cees; Mollnes, Tom Eirik; Tedesco, Francesco; Würzner, Reinhard; Trouw, Leendert A.; Truedsson, Lennart; Daha, Mohamed R.; Roos, Anja; Seelen, Marc A. (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-11-20)
      <p><i>Introduction</i>: The complement system is essential for an adequate immune response. Much attention has been given to the role of complement in disease. However, to better understand complement in pathology, it is crucial to first analyze this system under different physiological conditions. The aim of the present study was therefore to investigate the inter-individual variation in complement ...
    • 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, ...
    • 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 ...
    • The allosteric modulation of complement c5 by knob domain peptides 

      Macpherson, Alex; Laabei, Maisem; Ahdash, Zainab; Graewert, Melissa Ann; Birtley, James R.; Schulze, Monika-Sarah E.D.; Crennell, Susan; Robinson, Sarah A.; Holmes, Ben; Oleinikovas, Vladas; Nilsson, Per H.; Snowden, James; Ellis, Victoria; Mollnes, Tom Eirik; Deane, Charlotte M.; Svergun, Dmitri I.; Lawson, Alastair D.G.; van den Elsen, Jean (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-02-11)
      Bovines have evolved a subset of antibodies with ultra-long heavy chain complementarity determining regions that harbour cysteine-rich knob domains. To produce high-affinity peptides, we previously isolated autonomous 3–6 kDa knob domains from bovine antibodies. Here, we show that binding of four knob domain peptides elicits a range of effects on the clinically validated drug target complement C5. ...
    • The Alternative Complement Pathway Is Activated Without a Corresponding Terminal Pathway Activation in Patients With Heart Failure 

      Shahini, Negar; Bjørkelund, Elisabeth; Bendz, Christina; Massey, Richard J; Schjalm, Camilla; Halvorsen, Bente; Broch, Kaspar; Ueland, Thor; Gullestad, Lars; Nilsson, Per H.; Aukrust, Pål; Mollnes, Tom Eirik; Louwe, Maria Cornelia; Holt, Margrethe Flesvig; Michelsen, Annika E. (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-24)
      Objective: Dysregulation of the complement system has been described in patients with heart failure (HF). However, data on the alternative pathway are scarce and it is unknown if levels of factor B (FB) and the C3 convertase C3bBbP are elevated in these patients. We hypothesized that plasma levels of FB and C3bBbP would be associated with disease severity and survival in patients with ...
    • The alternative complement pathway is dysregulated in patients with chronic heart failure 

      Shahini, Negar; Michelsen, Annika E.; Nilsson, Per H.; Ekholt, Karin; Gullestad, Lars; Broch, Kaspar; Dahl, Christen P.; Aukrust, Pål; Ueland, Thor; Mollnes, Tom Eirik; Yndestad, Arne; Louwe, Mieke C. (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-02-14)
      The complement system, an important arm of the innate immune system, is activated in heart failure (HF). We hypothesized that HF patients are characterized by an imbalance of alternative amplification loop components; including properdin and complement factor D and the alternative pathway inhibitor factor H. These components and the activation product, terminal complement complex (TCC), were measured ...
    • Anti-inflammatory effects of non-statin low-density lipoprotein cholesterol-lowering drugs: an unused potential? 

      Hovland, Anders; Retterstøl, Kjetil; Mollnes, Tom Eirik; Halvorsen, Bente Evy; Aukrust, Pål; Lappegård, Knut Tore (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-05)
      <i>Objectives</i>: Inflammatory responses are closely knit with low-density lipoprotein (LDL)-cholesterol in driving atherosclerosis. Even if LDL-cholesterol is causative to atherosclerotic diseases and LDL-cholesterol lowering reduces hard clinical endpoints, there is a residual risk for clinical events, possibly driven by inflammatory processes, in accordance with its role in autoimmune ...
    • Antirheumatic therapy is associated with reduced complement activation in rheumatoid arthritis 

      Nguyen, Thao; Hokstad, Ingrid; Fagerland, Morten; Mollnes, Tom Eirik; Hollan, Ivana; Feinberg, Mark W.; Hjeltnes, Gunnbjørg; Eilertsen, Gro Østli; Mikkelsen, Knut; Agewall, Stefan (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-02-25)
      Background The complement system plays an important role in pathophysiology of cardiovascular disease (CVD), and might be involved in accelerated atherogenesis in rheumatoid arthritis (RA). The role of complement activation in response to treatment, and in development of premature CVD in RA, is limited. Therefore, we examined the effects of methotrexate (MTX) and tumor necrosis factor inhibitors ...
    • 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 ...
    • 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 ...
    • Avoiding ambient air in test tubes during incubations of human whole-blood minimizes complement background activation 

      Storm, Benjamin; Christiansen, Dorte; Mollnes, Tom Eirik; Nielsen, Erik Waage (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-10-06)
      <p><i>Background - </i>In vitro, the complement system can be studied in test tubes incubated with anticoagulated human whole-blood. Background activation of complement may mask inflammatory signals. Air bubbles are known to activate complement. We examined if removing ambient air from test tubes before incubation reduced background complement activation. <p><i>Methods - </i>Blood from twelve donors ...
    • Biphasic release of the alarmin high mobility group box 1 protein early after trauma predicts poor clinical outcome 

      Ottestad, William Arne; Rognes, Ingrid Nygren; Pischke, Søren; Mollnes, Tom Eirik; Andersson, Ulf; Eken, Torsten (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08)
      <i>Objective</i>: The causal role of the prototype alarmin high mobility group box 1 protein (HMGB1) in systemic inflammation and remote organ injury after trauma and shock is established in animal models but not in humans. Our aim was therefore to determine HMGB1 concentration kinetics with high time resolution during the first hours after trauma in individual patients, and investigate the ...
    • 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 ...
    • Bradykinin-Induced Shock Increase Exhaled Nitric Oxide, Complement Activation and Cytokine Production in Pigs 

      Seip, Knut Fredrik; Evjenth, Bjørg; Hovland, Anders; Dybwik, Knut Gustav; Johansen, Harald Thidemann; Fure, Hilde; Mollnes, Tom Eirik; Nielsen, Erik Waage (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-03-04)
      Bradykinin is an important mediator in blood pressure regulation, ischemic precondition and capillary leakage, allergy, anaphylaxis, inflammation, and nociception, at least partly via the generation of nitric oxide (NO). Macrophages are particularly abundant in the porcine lung circulation. Upon bradykinin binding macrophages release cytokines and endothelial ...
    • Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes 

      Wibroe, Peter Popp; Anselmo, Aaron C; Nilsson, Per; Sarode, Apoorva; Gupta, Vivek; Urbanics, Rudolf; Szebeni, Janos; Hunter, Alan Christy; Mitragotri, Samir; Mollnes, Tom Eirik; Moghimi, Seyed Moein (Journal article; Manuskript; Tidsskriftartikkel; Peer reviewed; Preprint, 2017-04-10)
      Intravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust ...
    • C-reactive protein levels and depression in older and younger adults - A study of 19,947 individuals. The Tromsø study 

      Bugge, Erlend; Wynn, Rolf; Mollnes, Tom Eirik; Reitan, Solveig Merete Klæbo; Lapid, Maria I.; Grønli, Ole Kristian (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-12-17)
      In recent years, a connection between depression and inflammation has been established, with a range of immunological changes, both cellular and humoral, presenting during depressive states (Beydoun et al., 2016; Haapakoski et al., 2015; Wium-Andersen et al., 2013). Furthermore, there seems to be a dose-response relationship between depression and inflammation, in the sense that the more severe the ...