• 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 ...
    • Increased complement activation 3 to 6 h after trauma is a predictor of prolonged mechanical ventilation and multiple organ dysfunction syndrome: a prospective observational study 

      Rognes, Ingrid Nygren; Pischke, Søren Erik; Ottestad, William; Røislien, Jo; Berg, Jens Petter; Johnson, Christina; Eken, Torsten; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-08)
      Background - Complement activation is a central mechanism in systemic inflammation and remote organ dysfunction following major trauma. Data on temporal changes of complement activation early after injury is largely missing. We aimed to describe in detail the kinetics of complement activation in individual trauma patients from admission to 10 days after injury, and the association with trauma ...
    • Platelet-depletion of whole blood reveals that platelets potentiate the release of IL-8 from leukocytes Into plasma in a thrombin-dependent manner 

      Quach, Huy Quang; Johnson, Christina; Ekholt, Karin; Islam, Rakibul; Mollnes, Tom Eirik; Nilsson, Per (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-04)
      Objective: In a recent study, we found an elevated level of interleukin 8 (IL-8) in response to bacterial incubation in thrombin-sufficient human whole blood anticoagulated by the fibrin polymerization blocking peptide GPRP. Whether thrombin directly activated leukocytes or mediated the release via thrombin-dependent activation of platelets remains unresolved. Herein, we addressed the role of ...
    • Properdin binding to complement activating surfaces depends on initial C3b deposition 

      Harboe, Morten; Johnson, Christina; Nymo, Stig Haugset; Ekholt, Karin; Schjalm, Camilla; Lindstad, Julie Katrine; Pharo, Anne Margrethe; Hellerud, Bernt C; Ekdahl, Kristina Nilsson; Mollnes, Tom Eirik; Nilsson, Per (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-01-09)
      Two functions have been assigned to properdin; stabilization of the alternative convertase, C3bBb, is well accepted, whereas the role of properdin as pattern recognition molecule is controversial. The presence of nonphysiological aggregates in purified properdin preparations and experimental models that do not allow discrimination between the initial binding of properdin and binding secondary to C3b ...
    • 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 ...