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Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock
Orrem, Hilde Lang; Nilsson, Per; Pischke, Søren Erik; Grindheim, Guro; Garred, Peter; Seljeflot, Ingebjørg; Husebye, Trygve Guttorm; Aukrust, Pål; Yndestad, Arne; Andersen, Geir Øystein; Barratt-Due, Andreas; Mollnes, Tom Eirik (Journal article; Peer reviewed, 2018)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. Methods and ... -
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; Peer reviewed, 2018)Introduction: 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 ... -
Alginate microbeads are coagulation compatible, while alginate microcapsules activate coagulation secondary to complement or directly through FXII
Gravastrand, Caroline; Hamad, Shamal; Fure, Hilde; Steinkjer, Bjørg; Ryan, Liv; Oberholzer, José; Lambris, John D.; Lacík, Igor; Mollnes, Tom Eirik; Brekke, Ole-Lars; Rokstad, Anne Mari (Journal article; Peer reviewed, 2017)Alginate microspheres are presently under evaluation for future cell-based therapy. Their ability to induce harmful host reactions needs to be identified for developing the most suitable devices and efficient prevention ... -
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; 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 ... -
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; Peer reviewed, 2016)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 ... -
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 (Peer reviewed; Journal article, 2020)Objectives. 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 ... -
Biocompatibility and Biotolerability Assessment of Microspheres Using a Whole Blood Model
Rokstad, Anne Mari; Strand, Berit Løkensgard; Espevik, Terje; Mollnes, Tom Eirik (Journal article, 2013)The whole blood model is a powerful method to determine the immediate inflammatory reactions towards foreign objects in general. This review focuses on the use of a lepirudin based whole blood model for evaluating microspheres ... -
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; Peer reviewed, 2019)Objectives: The causal role of the prototype alarmin high mobility group box 1 protein in systemic inflammation and remote organ injury after trauma and shock is established in animal models but not in humans. Our aim ... -
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, 2017)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 ... -
C-C Motif Ligand 20 (CCL20) and C-C Motif Chemokine Receptor 6 (CCR6) in Human Peripheral Blood Mononuclear Cells: Dysregulated in Ulcerative Colitis and a Potential Role for CCL20 in IL-1β Release
Skovdahl, Helene Kolstad; Damås, Jan Kristian; Granlund, Atle van Beelen; Østvik, Ann Elisabet; Doseth, Berit; Bruland, Torunn; Mollnes, Tom Eirik; Sandvik, Arne Kristian (Journal article; Peer reviewed, 2018)The chemokine C-C motif ligand 20 (CCL20) is increased in the colonic mucosa during active inflammatory bowel disease (IBD) and can be found both in the epithelium and immune cells in the lamina propria. The present study ... -
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, 2015)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 ... -
Changes in cytokines during treatment of elderly, hospitalized psychiatric patients - a naturalistic study
Bugge, Erlend; Wynn, Rolf; Mollnes, Tom Eirik; Reitan, Solveig Merete Klæbo; Lapid, Maria; Grønli, Ole Kristian (Journal article; Peer reviewed, 2019)Immunological abnormalities have been demonstrated in several psychiatric disorders. Predominantly, studies have focused on younger adults, and research on elderly psychiatric in-patients is scant. In this naturalistic ... -
Chimeric Anti-CD14 IGG2/4 Hybrid Antibodies for Therapeutic Intervention in Pig and Human Models of Inflammation
Lau, Corinna; Gunnarsen, Kristin Støen; Høydahl, Lene Støkken; Andersen, Jan Terje; Berntzen, Gøril; Pharo, Anne Margrethe; Lindstad, Julie Katrine; Ludviksen, Judith K; Brekke, Ole Lars; Barratt-Due, Andreas; Nielsen, Erik Waage; Stokes, Christopher R.; Espevik, Terje; Sandlie, Inger; Mollnes, Tom Eirik (Journal article; Peer reviewed, 2013)CD14 is a key recognition molecule of innate immune responses, interacting with several TLRs. TLR signaling cross-talks extensively with the complement system, and combined CD14 and complement inhibition has been proved ... -
Cholesterol crystal-induced endothelial cell activation is complement-dependent and mediated by TNF
Nymo, Stig Haugset; Niyonzima, Nathalie; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Peer reviewed, 2014)Cholesterol crystals are known to be a hallmark of atherosclerosis with recent studies demonstrating deposition of these crystals in early fatty streak formation as well as penetrating the intima following plaque rupture. ... -
Cholesterol crystals activate the lectin complement pathway via ficolin-2 and mannose-binding lectin: Implications for the progression of atherosclerosis
Pilely, Katrine; Rosbjerg, Anne; Genster, Ninette; Gál, Peter; Pál, Gábor; Halvorsen, Bente; Holm, Sverre; Aukrust, Pål; Bakke, Siril Skaret; Sporsheim, Bjørnar; Nervik, Ingunn; Niyonzima, Nathalie; Bartels, Emil D.; Stahl, Gregory L.; Mollnes, Tom Eirik; Espevik, Terje; Garred, Peter (Journal article, 2016)Cholesterol crystals (CC) play an essential role in the formation of atherosclerotic plaques. CC activate the classical and the alternative complement pathways, but the role of the lectin pathway is unknown. We hypothesized ... -
Cholesterol Crystals Induce coagulation Activation through Complement-Dependent Expression of Monocytic Tissue Factor
Gravastrand, Caroline S.; Steinkjer, Bjørg; Halvorsen, Bente; Landsem, Anne; Skjelland, Mona; Jacobsen, Eva Astrid; Woodruff, Trent M.; Lambris, John D.; Mollnes, Tom Eirik; Brekke, Ole-Lars; Espevik, Terje; Rokstad, Anne Mari (Journal article; Peer reviewed, 2019)Cholesterol crystals (CC) are strong activators of complement and could potentially be involved in thromboinflammation through complement-coagulation cross-talk. To explore the coagulation-inducing potential of CC, we ... -
Cholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosis
Niyonzima, Nathalie; Bakke, Siril S.; Gregersen, Ida; Holm, Sverre; Sandanger, Øystein; Orrem, Hilde Lang; Sporsheim, Bjørnar; Ryan, Liv; Kong, Xiang Yi; Dahl, Tuva Børresdatter; Skjelland, Mona; Sørensen, Kirsten; Rokstad, Anne Mari A.; Yndestad, Arne; Latz, Eicke; Gullestad, Lars; Andersen, Geir Øystein; Damås, Jan Kristian; Aukrust, Pål; Mollnes, Tom Eirik; Halvorsen, Bente; Espevik, Terje (Peer reviewed; Journal article, 2020)Background: During atherogenesis, cholesterol precipitates into cholesterol crystals (CC) in the vessel wall, which trigger plaque inflammation by activating the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) ... -
Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome
Thomas, Anub Mathew; Schjalm, Camilla; Nilsson, Per; Lindenskov, Paal Helge H.; Rørtveit, Runa; Solberg, Rønnaug; Saugstad, Ola Didrik; Berglund, Magnus M.; Strömberg, Patrik; Lau, Corinna; Espevik, Terje; Jansen, Johan Høgset; Castellheim, Albert; Mollnes, Tom Eirik; Barratt-Due, Andreas (Journal article; Peer reviewed, 2018)Background: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a ... -
Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis
Hellerud, Bernt C; Orrem, Hilde L.; Dybwik, Knut Gustav; Pischke, Søren Erik; Barratt-Due, Andreas; Castellheim, Albert; Fure, Hilde; Bergseth, Grete; Christiansen, Dorte; Nunn, Miles A.; Espevik, Terje; Lau, Corinna; Brandtzæg, Petter; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Peer reviewed, 2017)Background Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key ... -
Combined inhibition of complement and CD14 attenuates bacteria-induced inflammation in human whole blood more efficiently than antagonizing the toll-like receptor 4-MD2 complex
Gustavsen, Alice; Nymo, Stig Haugset; Landsem, Anne; Christiansen, Dorte; Ryan, Liv; Husebye, Harald; Lau, Corinna; Pischke, Søren Erik; Lambris, John D.; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Peer reviewed, 2016)Background. Single inhibition of the Toll-like receptor 4 (TLR4)–MD2 complex failed in treatment of sepsis. CD14 is a coreceptor for several TLRs, including TLR4 and TLR2. The aim of this study was to investigate the effect ...