Article
Immunology
Benjamin S. Storm, Judith K. Ludviksen, Dorte Christiansen, Hilde Fure, Kristin Pettersen, Anne Landsem, Bent Aksel Nilsen, Knut Dybwik, Tonje Braaten, Erik W. Nielsen, Tom E. Mollnes
Summary: This study aimed to investigate the effects of air embolism on thromboinflammation in pigs. The results showed that air embolism caused an increase in white blood cell count, activation of C3, and alterations in hemostatic parameters. Additionally, it triggered the release of cytokines in lung tissue. The study suggests that C3 inhibition may represent a therapeutic approach to attenuate the response.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Hongmei Yang, Chang-ki Oh, Haitham Amal, John S. Wishnok, Sarah Lewis, Emily Schahrer, Dorit Trudler, Tomohiro Nakamura, Steven R. Tannenbaum, Stuart A. Lipton
Summary: Protein S-nitrosylation plays a crucial role in various processes in health and disease, and it is implicated in synaptic damage in Alzheimer's disease. By studying SNO proteins in AD brains, we found that the formation of SNO-C3 is sex-dependent and may contribute to cognitive decline through increased synaptic phagocytosis.
Article
Immunology
Martina Bonacini, Ilaria Ferrigno, Alessandro Rossi, Nicola Facciolongo, Marco Massari, Romina Corsini, Veronica Galli, Alessandro Zerbini, Carlo Salvarani, Stefania Croci
Summary: This study aimed to identify differences in cytokine release by T cells ex-vivo between COVID-19 patients with diverse disease severity. The results showed differences in cytokine release between patients of different disease severity, but these differences do not seem to explain the need for non-invasive ventilation.
Article
Nutrition & Dietetics
Annie Lauer, Markus Burkard, Heike Niessner, Christian Leischner, Olga Renner, Claudia Vollbracht, Holger Michels, Christian Busch, Tobias Sinnberg, Sascha Venturelli
Summary: Sepsis is a complex clinical syndrome with an excessive inflammatory response, where vitamin C deficiency plays a crucial role. Research shows that high-dose vitamin C, either alone or in combination with other drugs, can effectively reduce cytokine response and potentially improve the condition of sepsis patients.
Article
Immunology
Paul D. Bates, Alexander L. Rakhmilevich, Monica M. Cho, Myriam N. Bouchlaka, Seema L. Rao, Joanna M. Hales, Rimas J. Orentas, Terry J. Fry, Stephen D. Gilles, Paul M. Sondel, Christian M. Capitini
Summary: Using allogeneic hematopoietic stem cell transplant (HSCT) for high-risk neuroblastoma (NBL) can increase survival rates, and combining specific immunocytokines and ex vivo activated NK cells can control tumor growth, decrease peripheral effector cell subsets, but must be balanced with the risk of inducing cytokine release syndrome (CRS).
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Viktoriia Chaban, Eline de Boer, Karin E. McAdam, Jarle Vaage, Tom Eirik Mollnes, Per H. Nilsson, Soren Erik Piscike, Rakibul Islam
Summary: Systemic inflammatory conditions are often linked to abnormal body temperatures. A study investigated the effect of different temperatures on the inflammatory response and found that higher temperatures led to increased complement activation. Additionally, the study showed that cytokine production was influenced by temperature, with the highest levels occurring at 39°C.
MOLECULAR IMMUNOLOGY
(2023)
Review
Immunology
Tom E. Mollnes, Benjamin S. Storm, Ole L. Brekke, Per H. Nilsson, John D. Lambris
Summary: The complement system, initially thought to protect the host from infection, has been shown to have numerous other functions and plays a major role in various diseases. Traditional reductionistic models of complement research are limited, and there is a need for holistic models that retain complement activity and allow for the study of interactions with other inflammatory systems. Two such models using anticoagulated whole blood are described here, which will be useful in further understanding complement-driven diseases.
SEMINARS IN IMMUNOLOGY
(2022)
Article
Medical Laboratory Technology
Rhys T. Meredith, Ross A. R. Yarham, Hayley Mills, Maria A. Oliver
Summary: The study found that capillary blood draw via a microneedle device yields immune responses comparable to venipuncture at baseline and following peptide stimulation, suggesting it as a viable method for rapid whole blood cytokine release assays (CRAs). However, differential cytokine production is observed following capillary blood draw via finger prick.
CLINICAL BIOCHEMISTRY
(2023)
Article
Immunology
Andreas Tornell, Hanna Grauers Wiktorin, Johan Ringlander, Mohammad Arabpour, Malin R. Nilsson, Staffan Nilsson, Roberta Kiffin, Magnus Lindh, Martin Lagging, Kristoffer Hellstrand, Anna Martner
Summary: A whole-blood stimulation assay was developed to detect SARS-CoV-2-specific T cells in previously infected or vaccinated individuals. The study found that T-cell responses persisted longer than immunoglobulin G responses and could be used to evaluate complications and vaccine-induced T-cell immunity.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Immunology
Melinda Y. Hardy, Gautam Goel, Amy K. Russell, Swee Lin G. Chen Yi Mei, Gregor J. E. Brown, Suyue Wang, Evan Szymczak, Ruan Zhang, Kaela E. Goldstein, Kristin M. Neff, Leslie J. Williams, Kenneth E. Truitt, John L. Dzuris, Jason A. Tye-Din, Robert P. Anderson
Summary: Improved blood tests are needed to effectively monitor experimental therapies for coeliac disease by assessing the functional status of rare gluten-specific CD4+ T cells. Using fresh whole blood instead of PBMC significantly enhances cytokine secretion stimulated by gluten peptides, enabling assessment of rare antigen-specific T cells in clinical studies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Gergely Tibor Kozma, Tamas Meszaros, Tamas Bakos, Mark Hennies, Daniel Bencze, Barbara Uzonyi, Balazs Gyorffy, Edward Cedrone, Marina A. Dobrovolskaia, Mihaly Jozsi, Janos Szebeni
Summary: The study investigated the relationship between complement activation and cytokine storm using an in vitro model, suggesting a potential anti-CS and anti-inflammatory role of mini-factor H.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Christina Johnson, Huy Quang Quach, Corinna Lau, Karin Ekholt, Terje Espevik, Trent M. Woodruff, Soren Erik Pischke, Tom Eirik Mollnes, Per H. Nilsson
Summary: Thrombin plays an important role in inflammation, but studying its effects on thromboinflammatory responses is difficult in common experimental models. In this study, the anticoagulant peptide GPRP was used to investigate the effects of thrombin on acute inflammation caused by Escherichia coli and Staphylococcus aureus. The results showed that thrombin could modulate bacterial-induced inflammation and had differential effects on cytokine production.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
R. P. Anderson, G. Goel, M. Y. Hardy, A. R. Russell, S. Wang, E. Szymczak, R. Zhang, K. E. Goldstein, M. Neff, K. E. Truitt, L. J. Williams, J. L. Dzuris, J. A. Tye-Din
Summary: The study found that whole blood IL-2 release assay is effective in detecting immune responses to gliadin peptides, aiding in the diagnosis and monitoring of coeliac disease. Results showed that GC caused an increase in IL-2 release, indicating the dominant role of IL-2 in whole blood cytokine release assays.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2021)
Article
Immunology
M. Eltahir, E. Fletcher, L. Dynesius, J. L. Jarblad, M. Lord, I. Lauren, M. Zekarias, X. Yu, M. S. Cragg, C. Hammarstrom, K. H. Levedahl, M. Hoglund, G. Ullenhag, M. Mattsson, S. M. Mangsbo
Summary: The study using CLL patient blood demonstrated CDC and ADCC profiles along with depletion of CLL cells upon rituximab infusion. While B cell depletion and CRS were observed only in patients, inhibition of CDC or ADCC resulted in skewing of the immune killing mechanism. The human whole blood loop model can be applied to build disease-specific CRS and immune activation profiling ex vivo using blood from a specific indication.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Medicine, General & Internal
Husam Oudah Aljwaid, Thamer J. Ghali, Ali A. Al-Hisnawi, Kasim Sakran Abass
Summary: The study found elevated levels of IL6 in COVID-19 patients with cytokine storm, as well as increased levels of complement components C3 and C4. This suggests a correlation between cytokine storm and these immune system factors.
PAKISTAN JOURNAL OF MEDICAL & HEALTH SCIENCES
(2021)
Article
Oncology
Sergio Ortiz-Espinosa, Xabier Morales, Yaiza Senent, Diego Alignani, Beatriz Tavira, Irati Macaya, Borja Ruiz, Haritz Moreno, Ana Remirez, Cristina Sainz, Alejandro Rodriguez-Pena, Alvaro Oyarbide, Mikel Ariz, Maria P. Andueza, Karmele Valencia, Alvaro Teijeira, Kai Hoehlig, Axel Vater, Barbara Rolfe, Trent M. Woodruff, Jose Maria Lopez-Picazo, Silvestre Vicent, Grazyna Kochan, David Escors, Ignacio Gil-Bazo, Jose Luis Perez-Gracia, Luis M. Montuenga, John D. Lambris, Carlos Ortiz de Solorzano, Fernando Lecanda, Daniel Ajona, Ruben Pio
Summary: This study reveals that C5a can enhance the capacity of PMN-MDSCs to promote tumor growth and metastasis by inducing the formation of NETs. The formation of NETs is dependent on the production of HMGB1 by cancer cells. Inhibiting C5a, C5aR1, or NETosis can reduce the number of circulating tumor cells and the metastatic burden in a mouse lung metastasis model. The translational relevance of these findings is supported by the stimulation of migration and NETosis in PMN-MDSCs obtained from lung cancer patients.
Article
Critical Care Medicine
Relber A. Goncales, Helder Novais Bastos, Claudio Duarte-Oliveira, Daniela Antunes, Oksana Sokhatska, Maria Jacob, Rui Rolo, Claudia F. Campos, Sergio D. Sasaki, Alessia Donato, Sarah N. Mapelli, Sandra Costa, Conceicao Souto Moura, Luis Delgado, Antonio Morais, Egidio Torrado, Frank L. van de Veerdonk, Thomas Weichhart, John D. Lambris, Ricardo Silvestre, Cecilia Garlanda, Alberto Mantovani, Cristina Cunha, Agostinho Carvalho
Summary: This study reveals the role of long pentraxin PTX3 in sarcoidosis, finding that its deficiency can lead to amplified complement activation and promote granuloma formation. The results suggest that PTX3 plays a pivotal role in macrophages to restrain granulomatous inflammation and this signaling axis holds therapeutic potential for targeting granuloma formation in sarcoidosis.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Editorial Material
Immunology
Dimitrios C. Mastellos, John D. Lambris
SEMINARS IN IMMUNOLOGY
(2022)
Review
Endocrinology & Metabolism
Tanya S. McDonald, Titaya Lerskiatiphanich, Trent M. Woodruff, Pamela A. McCombe, John D. Lee
Summary: Neurodegeneration refers to the progressive loss of neurons in disorders like Alzheimer's, Huntington's, and Parkinson's disease. Energy metabolism disturbances and alterations are common features in the onset and progression of these diseases. Understanding these metabolic changes could lead to improved treatment options for neurodegenerative disorders.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Eduardo A. Albornoz, Alberto A. Amarilla, Naphak Modhiran, Sandra Parker, Xaria X. Li, Danushka K. Wijesundara, Julio Aguado, Adriana Pliego Zamora, Christopher L. D. McMillan, Benjamin Liang, Nias Y. G. Peng, Julian D. J. Sng, Fatema Tuj Saima, Jenny N. Fung, John D. Lee, Devina Paramitha, Rhys Parry, Michael S. Avumegah, Ariel Isaacs, Martin W. Lo, Zaray Miranda-Chacon, Daniella Bradshaw, Constanza Salinas-Rebolledo, Niwanthi W. Rajapakse, Ernst J. Wolvetang, Trent P. Munro, Alejandro Rojas-Fernandez, Paul R. Young, Katryn J. Stacey, Alexander A. Khromykh, Keith J. Chappell, Daniel Watterson, Trent M. Woodruff
Summary: COVID-19 infection may lead to neurological symptoms similar to Parkinson's disease. The study found that SARS-CoV-2 and spike protein can directly activate the NLRP3 inflammasome in microglial cells, which may contribute to the development of neuroinflammation.
MOLECULAR PSYCHIATRY
(2023)
Article
Pediatrics
Aline U. Bjerkhaug, Hildegunn N. Granslo, Jorunn Pauline Cavanagh, Ina Hoiland, Judith Krey Ludviksen, Corinna Lau, Terje Espevik, Tom Eirik Mollnes, Claus Klingenberg
Summary: Inhibition of both C5 and CD14 shows promise as a potential therapeutic approach for severe cases of neonatal sepsis, as it can effectively reduce bacterial-induced inflammation.
PEDIATRIC RESEARCH
(2023)
Article
Immunology
Xaria X. Li, John D. Lee, Han S. Lee, Richard J. Clark, Trent M. Woodruff
Summary: TLQP-21 is a neuropeptide derived from the VGF precursor protein and has pleiotropic roles in regulating metabolism, nociception, and microglial functions. TLQP-21 acts through several receptors, with C3aR being the most commonly reported. However, its activity in immune cells, which express C3aR, remains understudied. This study found that TLQP-21 induced ERK signaling in human and mouse macrophages, with mouse TLQP-21 being more potent than the human counterpart. These findings suggest a significant discrepancy in TLQP-21 C3aR activity between human and murine receptors in immune cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Charles Bayly-Jones, Bill H. T. Ho, Corinna Lau, Eleanor W. W. Leung, Laura D'Andrea, Christopher J. J. Lupton, Susan M. M. Ekkel, Hariprasad Venugopal, James C. C. Whisstock, Tom E. E. Mollnes, Bradley A. A. Spicer, Michelle A. A. Dunstone
Summary: The cryo-EM structure of monoclonal antibody aE11 bound to polyC9 reveals that the binding site within the Membrane Attack Complex is a quaternary discontinuous epitope formed by two separate surfaces of the oligomeric C9 periphery.
COMMUNICATIONS BIOLOGY
(2023)
Review
Hematology
Christina Lamers, Daniel Ricklin, John D. Lambris
Summary: The number of complement inhibitors approved for therapeutic use or in late-stage clinical trials has expanded rapidly in recent years. The sudden emergence of this area in biotech start-ups and pharmaceutical companies is surprising considering the well-established involvement of the complement system in various clinical conditions. However, the complement system has unique characteristics that have delayed its recognition as a traditional drug target, such as concerns about safety and the complexity of its involvement in biological processes.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
Andrew O. Yam, Jacqueline Bailey, Francis Lin, Arnolda Jakovija, Scott E. Youlten, Claudio Counoupas, Matthias Gunzer, Tobias Bald, Trent M. Woodruff, James A. Triccas, Leonard D. Goldstein, David Gallego-Ortega, Shane T. Grey, Tatyana Chtanova
Summary: Intratumoral injection of microbial bioparticles stimulates neutrophil antitumor functions, leading to remodeling of tumor tissue, repression of tumor growth, and enhancement of checkpoint inhibitor therapy. This indicates the potential of microbial therapy in the treatment of solid cancers.
Editorial Material
Cell Biology
Eduardo A. Albornoz, Richard Gordon, Vinod Kumar, Avril A. B. Robertson, Kate Schroder, Trent M. Woodruff
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Amelie Kuhn, Jana Riegger, Graciosa Q. Teixeira, Markus Huber-Lang, John D. Lambris, Cornelia Neidlinger-Wilke, Rolf E. Brenner
Summary: Terminal complement complex deposition was found in human degenerated discs. The study investigated the mechanisms and effects of terminal complement activation in annulus fibrosus (AF) cells. Complement inhibitors effectively suppressed anaphylatoxin generation and TCC deposition induced by zymosan. Gene expression of ADAMTS4, MMP1, and COX2 was influenced by C3 and C5 blockade. Degenerated endplate tissue secreted soluble factors that enhanced direct C5 cleavage. These findings suggest the functional involvement of terminal complement activation in disc degeneration and the role of degenerated tissue in complement activation.
Article
Biochemical Research Methods
Xaria X. Li, Trent M. Woodruff
Summary: This study presents a protocol for investigating the effects of C3aR and C5aR1 receptors in vitro using phosphorylated ERK as a readout. The protocol includes steps for isolating human monocyte-derived macrophages, culturing and preparing cell lines expressing the receptors, performing pharmacological assays, and detecting phospho-ERK1/2.
Article
Cell Biology
Julio Aguado, Alberto A. Amarilla, Atefeh Taherian Fard, Eduardo A. Albornoz, Alexander Tyshkovskiy, Marius Schwabenland, Harman K. Chaggar, Naphak Modhiran, Cecilia Gomez-Inclan, Ibrahim Javed, Alireza A. Baradar, Benjamin Liang, Lianli Peng, Malindrie Dharmaratne, Giovanni Pietrogrande, Pranesh Padmanabhan, Morgan E. Freney, Rhys Parry, Julian D. J. Sng, Ariel Isaacs, Alexander A. Khromykh, Guillermo Valenzuela Nieto, Alejandro Rojas-Fernandez, Thomas P. Davis, Marco Prinz, Bertram Bengsch, Vadim N. Gladyshev, Trent M. Woodruff, Jessica C. Mar, Daniel Watterson, Ernst J. Wolvetang
Summary: Senescent cells play a significant role in brain aging and COVID-19-induced neuropathology, and senolytic therapy shows therapeutic potential in protecting against COVID-19-induced brain aging.
Article
Immunology
Christina Johnson, Huy Quang Quach, Corinna Lau, Karin Ekholt, Terje Espevik, Trent M. Woodruff, Soren Erik Pischke, Tom Eirik Mollnes, Per H. Nilsson
Summary: Thrombin plays an important role in inflammation, but studying its effects on thromboinflammatory responses is difficult in common experimental models. In this study, the anticoagulant peptide GPRP was used to investigate the effects of thrombin on acute inflammation caused by Escherichia coli and Staphylococcus aureus. The results showed that thrombin could modulate bacterial-induced inflammation and had differential effects on cytokine production.
JOURNAL OF IMMUNOLOGY
(2022)