• 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 ...
    • 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 ...
    • Synthetic Oligodeoxynucleotide CpG Motifs Activate Human Complement through Their Backbone Structure and Induce Complement-Dependent Cytokine Release 

      de Boer, Eline; Sokolova, Marina; Quach, Huy Quang; Mc Adam, Karin Ekholt; Götz, Maximilian P.; Chaban, Viktoriia; Vaage, Ingvar Jarle; Fageräng, Beatrice Linnea Christina; Woodruff, Trent M.; Garred, Peter; Nilsson, Per; Mollnes, Tom Eirik; Pischke, Soeren (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-11-01)
      Bacterial and mitochondrial DNA, sharing an evolutionary origin, act as danger-associated molecular patterns in infectious and sterile inflammation. They both contain immunomodulatory CpG motifs. Interactions between CpG motifs and the complement system are sparsely described, and mechanisms of complement activation by CpG remain unclear. Lepirudin-anticoagulated human whole blood and plasma were ...
    • 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 ...