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1. Contributors

Author

Aiken, Catherine E.M., primary, Amiri, Azita, additional, Anderson, Faith L., additional, Argenson, Arthur, additional, Arita, Anna, additional, Attarian, Hrayr, additional, Berner, Alison, additional, Bhandari, Vineet, additional, Bhat, Vishwanath, additional, Bos, Angelo Jose Goncalves, additional, Bradbury, Neil A., additional, Bucher, Meghan L., additional, Burns, Jan, additional, Campesi, Ilaria, additional, Casadevall, Arturo, additional, Chiti, Hossein, additional, Christiansen, Dorte M., additional, Coad, Beth, additional, Corella, Dolores, additional, Coromilas, Ellie J., additional, de leon, Romina Garcia, additional, Devi-Chou, Virginia, additional, Dicent, Jocelyn, additional, Dorak, Mehmet Tevfik, additional, Einstein, Gillian, additional, Fajkovic, Harun, additional, Fang, Ferric C., additional, Fattore, Liana, additional, Fausto-Sterling, Anne, additional, Fazeli, Alireza, additional, Feldberg, Dov, additional, Fillingim, Roger B., additional, Franconi, Flavia, additional, Frith, Karen H., additional, Fritzen, Andreas M., additional, Fukui, Michika, additional, Galea, Liisa A.M., additional, Gazit, Dan, additional, Gazit, Zulma, additional, Gemmati, Donato, additional, Giblin, Josephine, additional, Glezerman, Marek, additional, Godakumara, Kasun, additional, Gram, Sydney, additional, Guillamon, Antonio, additional, Haga, Susanne B., additional, Hennessey, Jessica A., additional, Hihara, Masakatsu, additional, Holt, William V., additional, Hufnagel, Antonia, additional, Iwaguro, Hideki, additional, Jamialahmadi, Tannaz, additional, Joel, Daphna, additional, Jovanov, Emil, additional, Kakudo, Natsuko, additional, Kiens, Bente, additional, Kim, Jin Kyung, additional, Kirchengast, Sylvia, additional, Kochav, Stephanie M., additional, Kodithuwakku, Suranga P., additional, Kok, L.M., additional, Koopman, Peter, additional, Krut, Zoe, additional, Kuro, Atsuyuki, additional, Kuroda, Ryosuke, additional, Kushida, Satoshi, additional, Lai, Yunjia, additional, Lee, Bonnie H., additional, Lleo, Ana, additional, Lundsgaard, Anne-Marie, additional, Maggi, Adriana C., additional, Matsushita, Satoshi, additional, McCarthy, Margaret M., additional, Melloni, Alice, additional, Meloni, Maurizio, additional, Miller, Gary W., additional, Mishra, Suresh, additional, Mitsui, Toshihito, additional, Mizuno, Hiroshi, additional, Nelissen, R.G.H.H., additional, Nickl, Petr, additional, Nomura, Tatsuya, additional, Oertelt-Prigione, Sabine, additional, Oliveira-Zumda, Gabriela Guimaraes, additional, Ordovas, Jose M., additional, Parsamanesh, Negin, additional, Pelled, Gadi, additional, Puiu, Andrei A., additional, Rajah, M. Natasha, additional, Reddy, Doodipala Samba, additional, Reiner, Željko, additional, Sahebkar, Amirhossein, additional, Saita, Yoshitomo, additional, Sánchez-Serrano, Ibis, additional, Sari Motlagh, Reza, additional, Savic, Ivanka, additional, Schmidinger, Manuela, additional, Schmidt, Caleb M., additional, Schmidt, Michael A., additional, Sedlacek, Radislav, additional, Serani, Angelo, additional, Shaib, Fidaa, additional, Shariat, Shahrokh F., additional, Singh, Keshav K., additional, Sobajima, Satoshi, additional, Sokolowski, Dustin J., additional, Sokolowski, Marla B., additional, Sun, Simón(e) D., additional, Sun, Zhongxin, additional, Sung, Jihyun, additional, Syding, Linn Amanda, additional, Taneja, Veena, additional, Tautz, Diethard, additional, Thurston, Lisa M., additional, Tierney, Siobhan, additional, Tisato, Veronica, additional, Tobita, Morikuni, additional, Tollkuhn, Jessica, additional, Tsubosaka, Masanori, additional, Tucci, Valter, additional, Uribe, Carme, additional, Van Noort, A., additional, Votinov, Mikhail, additional, Walsh, Reubs J., additional, Wan, Elaine Y., additional, and Zubiaurre-Elorza, Leire, additional

Published
2023
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3. A novel selective leukocyte depletion human whole blood model reveals the specific roles of monocytes and granulocytes in the cytokine response to Escherichia coli.

Author

Fageräng, Beatrice, Lau, Corinna, Mc Adam, Karin Ekholt, Schjalm, Camilla, Christiansen, Dorte, Garred, Peter, Nilsson, Per H, and Mollnes, Tom Eirik

Subjects
GRANULOCYTES, TUMOR necrosis factors, LEUCOCYTES, MONOCYTES, ESCHERICHIA coli, CD14 antigen
Abstract

The lepirudin-based human whole blood model is a well-established ex vivo system to characterize inflammatory responses. However, the contribution of individual cell populations to cytokine release has not been investigated. Thus, we modified the model by selectively removing leukocyte subpopulations to elucidate their contribution to the inflammatory response. Lepirudin-anticoagulated whole blood was depleted from monocytes or granulocytes using StraightFrom Whole Blood MicroBeads. Reconstituted blood was incubated with Escherichia coli (108/mL) for 2 hours at 37 °C. CD11b, CD62P, and CD63 were detected by flow cytometry. Complement (C3bc, sC5b-9) and platelet activation (platelet factor 4, NAP-2) were measured by enzyme-linked immunosorbent assay. Cytokines were quantified by multiplex assay. A significant (P < 0.05) specific depletion of the monocyte (mean = 86%; 95% confidence interval = 71%–92%) and granulocyte (mean = 97%; 95% confidence interval = 96%–98%) population was obtained. Background activation induced by the depletion protocol was negligible for complement (C3bc and sC5b-9), leukocytes (CD11b), and platelets (NAP-2). Upon Escherichia coli incubation, release of 10 of the 24 cytokines was solely dependent on monocytes (interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-17A, interferon-γ, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-1α, and fibroblast growth factor–basic), whereas 8 were dependent on both monocytes and granulocytes (IL-1ra, IL-6, IL-8, IL-9, IL-10, macrophage inflammatory protein-1β, tumor necrosis factor, and eotaxin). Six cytokines were not monocyte or granulocyte dependent, of which platelet-derived growth factor and RANTES were mainly platelet dependent. We document an effective model for selective depletion of leukocyte subpopulations from whole blood, without causing background activation, allowing in-depth cellular characterization. The results are in accordance with monocytes playing a major role in cytokine release and expand our knowledge of the significant role of granulocytes in the response to E. coli. By selective removal of leukocyte subtypes from human blood, we were able to use a holistic approach to identify cells responsible for the cytokine release induced by Escherichia coli incubated in the whole blood model. [ABSTRACT FROM AUTHOR]

Published
2024
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8. SELVSKADE OG DIGITALE FÆLLESSKABER – EN TEMATISK ANALYSE AF POSITIVE OG NEGATIVE KONSEKVENSER.

Author

Christensen, Leah Garfield, Nielsen, Julie Krogh, Elklit, Ask, and Christiansen, Dorte Mølgaard

Abstract

Copyright of Psyke & Logos is the property of Dansk Psykologisk Forlag and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2024
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19. List of Contributors

Author

Aiken, Catherine E.M., primary, Allen, Nicholas B., additional, Aryal, Shambhu, additional, Attarian, Hrayr, additional, Avula, Uma Mahesh R., additional, Bolignano, Davide, additional, Bradbury, Neil A., additional, Burns, Jan, additional, Cahill, Larry, additional, Carcea, Ioana, additional, Chan, Yvonne Y., additional, Chang, Howard, additional, Charkoudian, Nisha, additional, Christiansen, Dorte M., additional, Coffey, Sharon Saunderson, additional, Coleman, Eli, additional, Cuttino, Marsh, additional, Dobs, Adrian, additional, Dorak, Mehmet Tevfik, additional, Drescher, Jack, additional, Ederer, Ines Ana, additional, Fazeli, Alireza, additional, Feldberg, Dov, additional, Fesseha, Betiel, additional, Fillingim, Roger B., additional, Frith, Karen H., additional, Fritzen, Andreas M., additional, Froemke, Robert C., additional, Fujimura, Juri, additional, Gazit, Dan, additional, Glezerman, Marek, additional, Goodwin, Thomas, additional, Guess, Tiffany, additional, Hackl, Florian, additional, Hadley, Kristie, additional, Haga, Susanne B., additional, Hart, Emma C., additional, Hiort, Olaf, additional, Hobert, Oliver, additional, Holt, William V., additional, Huisstede, B.M.A., additional, Hunter, Amy, additional, Hyakusoku, Hiko, additional, Jovanov, Emil, additional, Kakudo, Natsuko, additional, Kiens, Bente, additional, Kim, Jin Kyung, additional, Kok, Laura M., additional, Korn, Stephan M., additional, Kusumoto, Kenji, additional, Lin, Congxing, additional, Lleo, Ana, additional, Longmire, Michelle R., additional, Lundsgaard, Anne-Marie, additional, Ma, Liang, additional, Madhushri, Priyanka, additional, Mah, Leanna W., additional, Marson, Lesley, additional, McCarthy, Margaret M., additional, McClelland, Erin E., additional, Milenkovic, Aleksandar, additional, Mizuno, Hiroshi, additional, Morris, Shaun K., additional, Müller, Alexandra, additional, Nelissen, Rob G.H.H., additional, Nepal, Santosh K., additional, Nguyen, Claire K., additional, Nomura, Tatsuya, additional, Noonavath, Meghana, additional, Oertelt-Prigione, Sabine, additional, Ogawa, Rei, additional, Ono, Shimpei, additional, Orbay, Hakan, additional, Ordovas, Jose M., additional, Oren-Suissa, Meital, additional, Pauzenberger, Reinhard, additional, Pelled, Gadi, additional, Pisano, Anna, additional, Regitz-Zagrosek, Vera, additional, Sánchez-Serrano, Ibis, additional, Schmidt, Michael A., additional, Shaib, Fidaa, additional, Shapiro, Galina, additional, Shariat, Shahrokh F., additional, Sheiner, Eyal, additional, Simmons, Julian G., additional, Taneja, Veena, additional, Thurston, Lisa M., additional, Tierney, Siobhan, additional, Tobita, Morikuni, additional, Wan, Elaine, additional, Warwick, Kevin, additional, Wesselmann, Ursula, additional, Whittle, Sarah, additional, Yalamanchi, Swaytha, additional, and Yang, Jennifer H., additional

Published
2017
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21. Complement C3b contributes to Escherichia coli-induced platelet aggregation in human whole blood

Author

Landsem, Anne, Emblem, Ase, Lau, Corinna, Christiansen, Dorte, Gerogianni, Alexandra, Karlsen, Bard Ove, Mollnes, Tom Eirik, Nilsson, Per H., Brekke, Ole-Lars, Landsem, Anne, Emblem, Ase, Lau, Corinna, Christiansen, Dorte, Gerogianni, Alexandra, Karlsen, Bard Ove, Mollnes, Tom Eirik, Nilsson, Per H., and Brekke, Ole-Lars

Abstract

Introduction: Platelets have essential functions as first responders in the immune response to pathogens. Activation and aggregation of platelets in bacterial infections can lead to life-threatening conditions such as arterial thromboembolism or sepsis-associated coagulopathy. Methods: In this study, we investigated the role of complement in Escherichia coli (E. coli)-induced platelet aggregation in human whole blood, using Multiplate(R) aggregometry, flow cytometry, and confocal microscopy. Results and Discussion: 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 antibody significantly reduced the E. coli-induced platelet aggregation by 67% (p = 0.0133). We could not detect opsonized C3b on platelets, indicating that the effect of C3 was not dependent on C3b-fragment deposition on platelets. Indeed, inhibition of glycoprotein IIb/IIIa (GPIIb/IIIa) and complement receptor 1 (CR1) showed that these receptors were involved in platelet aggregation. Furthermore, aggregation was more pronounced in hirudin whole blood than in hirudin platelet-rich plasma, indicating that E. coli-induced platelet aggregation involved other blood cells. In conclusion, the E. coli-induced platelet aggregation in human whole blood is partly C3b-dependent, and GPIIb/IIIa and CR1 are also involved in this process.

Published
2022
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24. Venous Air Embolism Activates Complement C3 Without Corresponding C5 Activation and Trigger Thromboinflammation in Pigs

Author

Storm, Benjamin S., Ludviksen, Judith K., Christiansen, Dorte, Fure, Hilde, Pettersen, Kristin, Landsem, Anne, Nilsen, Bent Aksel, Dybwik, Knut, Braaten, Tonje, Nielsen, Erik W., and Mollnes, Tom E.

Subjects
Inflammation, Thromboinflammation, Interleukin-6, Swine, Interleukin-8, Immunology, Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711 [VDP], Thrombosis, Complement C3, Complement Membrane Attack Complex, Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk immunologi: 716 [VDP], Animals, Cytokines, Embolism, Air, Immunology and Allergy
Abstract

IntroductionAir embolism may complicate invasive medical procedures. Bubbles trigger complement C3-mediated cytokine release, coagulation, and platelet activationin vitroin human whole blood. Since these findings have not been verifiedin vivo, we aimed to examine the effects of air embolism in pigs on thromboinflammation.MethodsForty-five landrace pigs, average 17 kg (range 8.5-30), underwent intravenous air infusion for 300 or 360 minutes (n=29) or served as sham (n=14). Fourteen pigs were excluded due to e.g. infections or persistent foramen ovale. Blood was analyzed for white blood cells (WBC), complement activation (C3a and terminal C5b-9 complement complex [TCC]), cytokines, and hemostatic parameters including thrombin-antithrombin (TAT) using immunoassays and rotational thromboelastometry (ROTEM). Lung tissue was analyzed for complement and cytokines using qPCR and immunoassays. Results are presented as medians with interquartile range.ResultsIn 24 pigs receiving air infusion, WBC increased from 17×109/L (10-24) to 28 (16-42) (pConclusionVenous air embolism in pigs activated C3 without a corresponding C5 activation and triggered thromboinflammation, consistent with a C3-dependent mechanism. C3-inhibition might represent a therapeutic approach to attenuate this response.

Published
2022

28. Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood

Author

Storm, Benjamin S., primary, Christiansen, Dorte, additional, Fure, Hilde, additional, Ludviksen, Judith K., additional, Lau, Corinna, additional, Lambris, John D., additional, Woodruff, Trent M., additional, Brekke, Ole-Lars, additional, Braaten, Tonje, additional, Nielsen, Erik W., additional, and Mollnes, Tom Eirik, additional

Published
2021
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32. Vitamin C, Hydrocortisone, and the Combination Thereof Significantly Inhibited Two of Nine Inflammatory Markers Induced by Escherichia Coli But Not by Staphylococcus Aureus – When Incubated in Human Whole Blood

Author

Medeiros, Pedro Miguel Coelho, primary, Schjalm, Camilla, additional, Christiansen, Dorte, additional, Sokolova, Marina, additional, Pischke, Soeren Erik, additional, Würzner, Reinhard, additional, Mollnes, Tom Eirik, additional, and Barratt-Due, Andreas, additional

Published
2021
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33. Quantification of Porcine Complement Activation Fragment C3a by a Neoepitope-Based Enzyme-Linked Immunosorbent Assay

Author

Nilsson, Per H., Pettersen, Kristin, Oppermann, Martin, Skjeflo, Espen W., Fure, Hilde, Christiansen, Dorte, Mollnes, Tom Eirik, Nilsson, Per H., Pettersen, Kristin, Oppermann, Martin, Skjeflo, Espen W., Fure, Hilde, Christiansen, Dorte, and Mollnes, Tom Eirik

Abstract

Enzyme-linked immunosorbent assay (ELISA) enables fast and simple quantification of analytes in the pico- to nanogram range in complex samples. Here, we describe an ELISA for the detection of porcine C3a as a marker for complement activation. Antibody specificity is critical for a robust assay. This assay is based on a pair of antibodies specific for the porcine C3a molecule and thus does not react with native C3.

Published
2021
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35. The role of age and mode of delivery in the STEPS intervention:A longitudinal pilot-study in treatment of posttraumatic stress symptoms in Danish survivors of sexual assault

Author

Vang, Maria Louison, Al Ali, Sara, Christiansen, Dorte Mølgaard, Dokkedahl, Sarah Bøgelund, and Elklit, Ask

Subjects
treatment, ICD-11, Intervention, PTSD, STEPS, rape, Sexual assault, CPTSD
Abstract

Background: The STEPS programme has been succesfully implemented as a group-based treatment of trauma symptoms after rape for adolescents. The STEPS intervention was translated from Dutch to Danish and offered to adults in addition to adolescents as well as an individual intervention in addition to a group-based intervention at a Danish Centre for Rape Victims through 2011 to 2014. The programme was translated from Dutch to Danish and expanded to adults in addition to adolescents as well as to an individual intervention in addition to a group-based intervention at a Danish Centre for Rape Victims through 2011 to 2014. Objective: The present study observes development in trauma symptoms and ICD-11 diagnostic status during an adapted version of the intervention programme ‘STEPS’ for survivors of sexual assault. Methods: A prospective uncontrolled study was conducted, monitoring symptoms of posttraumatic stress and other trauma-related symptomatology before treatment, after treatment and at 6 and 12 months' follow up for 103 referrals receiving individual or group-based STEPS. Tentative diagnoses of posttraumatic stress disorder (PTSD) and complex PTSD were assigned to participants according to the ICD-11 to observe the development in diagnostic status across time, and multilevel modelling was used to assess the development of symptom severity and to assess the moderating effect of age-group and mode of delivery. Results: A loglinear function representing large and statistically significant decline in symptomatology over time provided the best fit for all measures of trauma-related symptomatology. The decline was not moderated by age-group or mode of intervention. Dropout rates were independent of mode of intervention and age. Conclusion: The adaption of the STEPS programme to adults and as an individual intervention is feasible and maintains effect sizes comparable to those observed in the original intervention. Further research using randomized controlled trials is needed to ascribe the observed effect to the STEPS programme.

Published
2020

37. A Complement C3–Specific Nanobody for Modulation of the Alternative Cascade Identifies the C-Terminal Domain of C3b as Functional in C5 Convertase Activity

Author

Pedersen, Henrik, primary, Jensen, Rasmus K., additional, Jensen, Jens Magnus B., additional, Fox, Rachel, additional, Pedersen, Dennis V., additional, Olesen, Heidi G., additional, Hansen, Annette G., additional, Christiansen, Dorte, additional, Mazarakis, Sofia M. M., additional, Lojek, Neal, additional, Hansen, Pernille, additional, Gadeberg, Trine A. F., additional, Zarantonello, Alessandra, additional, Laursen, Nick S., additional, Mollnes, Tom Eirik, additional, Johnson, Matthew B., additional, Stevens, Beth, additional, Thiel, Steffen, additional, and Andersen, Gregers R., additional

Published
2020
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44. Comparison of cytokine changes in three different lipoprotein apheresis systems in an ex vivo whole blood model.

Author

Hardersen, Randolf, Enebakk, Terje, Christiansen, Dorte, Ludviksen, Judith K., Mollnes, Tom E., Lappegård, Knut Tore, and Hovland, Anders

Subjects
PLATELET-derived growth factor, VASCULAR endothelial growth factors, MONOCYTE chemotactic factor, TUMOR necrosis factors, DEXTRAN, DEXTRAN sulfate
Abstract

Introduction: Even if proprotein convertase subtilisin/kexin type 9 inhibitors have replaced lipoprotein apheresis in many patients, lipoprotein apheresis still is an important option in homozygous familial hypercholesterolemia, progressive atherosclerosis or when removal of lipoprotein(a) is indicated. Additional possible favorable effects beyond lipid lowering could include changes in the concentration of cytokines and improvement of hemorheology. Methods: We evaluated how whole blood adsorption, dextran sulfate plasma adsorption, and double filtration plasmapheresis lipoprotein apheresis systems affected cytokine concentrations, using a human whole blood ex vivo model differentiating the effect of the lipoprotein apheresis and plasma separation columns and describing temporal changes. Results: Compared to the control bag, the whole blood adsorption system reduced Interferon‐γ (IFN‐γ), IL‐8, IL‐1ra, eotaxin, tumor necrosis factor (TNF), monocyte chemoattractant protein 1 (MCP‐1), platelet derived growth factor (PDGF)‐BB, regulated on activation T cell expressed and secreted (RANTES), macrophage inflammatory protein‐1β (MIP‐1β), and IP‐10 (P <.05). The dextran sulfate plasma adsorption system reduced IFN‐γ, IL‐8, IL‐1ra, eotaxin, TNF, MCP‐1, PDGF‐BB, MIP‐1β, and IP‐10 (P <.05). Vascular endothelial growth factor (VEGF) and granulocyte macrophage colony stimulating factor (GM‐CSF) were increased in the whole blood and dextran sulfate plasma adsorption systems (P <.05). The double filtration plasmapheresis system reduced IFN‐γ, IL‐1ra, TNF, MIP‐1β, and IP‐10 (P <.05), while MCP‐1,VEGF, GM‐CSF, and RANTES were increased (P <.05). The plasma separation column increased concentration of RANTES, and was a barrier to reduction of eotaxin. Temporal patterns of concentration change indicated first pass increase of PDGF‐BB and first pass reduction of IP‐10. Conclusion: There were marked differences in how the three systems affected total and temporal cytokine concentration changes in this in vitro model, as well as compared to former in vivo studies. [ABSTRACT FROM AUTHOR]

Published
2020
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49. Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis

Author

Hellerud, Bernt C., primary, Orrem, Hilde L., additional, Dybwik, Knut, additional, Pischke, Søren E., additional, Baratt-Due, Andreas, additional, Castellheim, Albert, additional, Fure, Hilde, additional, Bergseth, Grethe, additional, Christiansen, Dorte, additional, Nunn, Miles A., additional, Espevik, Terje, additional, Lau, Corinna, additional, Brandtzæg, Petter, additional, Nielsen, Erik W., additional, and Mollnes, Tom E., additional

Published
2017
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