keyword
https://read.qxmd.com/read/32909942/soluble-collectin-12-mediates-c3-independent-docking-of-properdin-that-activates-the-alternative-pathway-of-complement
#1
Ying Jie Ma, Jie Zhang, Lihong Song, Dennis V Pedersen, Anna Li, John D Lambris, Gregers Rom Andersen, Tom Eirik Mollnes, Peter Garred
Properdin stabilizes the alternative C3 convertase (C3bBb), whereas its role as pattern recognition molecule mediating complement activation is disputed for decades. Previously, we have found that soluble collectin-12 (sCL-12) synergizes complement alternative pathway (AP) activation. However, whether this observation is C3 dependent is unknown. By application of the C3-inhibitor Cp40, we found that properdin in normal human serum bound to Aspergillus fumigatus solely in a C3b dependent manner. Cp40 also prevented properdin binding when properdin-depleted serum reconstituted with purified properdin was applied, in analogy with the findings achieved by C3- depleted serum...
September 10, 2020: ELife
https://read.qxmd.com/read/32844416/current-understanding-of-periodontal-disease-pathogenesis-and-targets-for-host-modulation-therapy
#2
REVIEW
George Hajishengallis, Triantafyllos Chavakis, John D Lambris
Recent advances indicate that periodontitis is driven by reciprocally reinforced interactions between a dysbiotic microbiome and dysregulated inflammation. Inflammation is not only a consequence of dysbiosis but, via mediating tissue dysfunction and damage, fuels further growth of selectively dysbiotic communities of bacteria (inflammophiles), thereby generating a self-sustained feed-forward loop that perpetuates the disease. These considerations provide a strong rationale for developing adjunctive host-modulation therapies for the treatment of periodontitis...
October 2020: Periodontology 2000
https://read.qxmd.com/read/32815311/complement-modulation-reverses-pathology-in-y402h-retinal-pigment-epithelium-cell-model-of-age-related-macular-degeneration-by-restoring-lysosomal-function
#3
Edvinas Cerniauskas, Marzena Kurzawa-Akanbi, Long Xie, Dean Hallam, Marina Moya-Molina, Kathryn White, David Steel, Mary Doherty, Phil Whitfield, Jumana Al-Aama, Lyle Armstrong, David Kavanagh, John D Lambris, Viktor I Korolchuk, Claire Harris, Majlinda Lako
Age-related macular degeneration (AMD) is a multifactorial disease, which is characterized by loss of central vision, affecting one in three people by the age of 75. The Y402H polymorphism in the complement factor H (CFH) gene significantly increases the risk of AMD. We show that Y402H-AMD-patient-specific retinal pigment epithelium (RPE) cells are characterized by a significant reduction in the number of melanosomes, an increased number of swollen lysosome-like-vesicles with fragile membranes, Cathepsin D leakage into drusen-like deposits and reduced lysosomal function...
August 20, 2020: Stem Cells Translational Medicine
https://read.qxmd.com/read/32759504/complement-and-tissue-factor-enriched-neutrophil-extracellular-traps-are-key-drivers-in-covid-19-immunothrombosis
#4
Panagiotis Skendros, Alexandros Mitsios, Akrivi Chrysanthopoulou, Dimitrios C Mastellos, Simeon Metallidis, Petros Rafailidis, Maria Ntinopoulou, Eleni Sertaridou, Victoria Tsironidou, Christina Tsigalou, Maria G Tektonidou, Theocharis Konstantinidis, Charalampos Papagoras, Ioannis Mitroulis, Georgios Germanidis, John D Lambris, Konstantinos Ritis
Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyper-inflammation and thrombotic microangiopathy, thereby increasing COVID-19 mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies and NETs/human aortic endothelial cell (HAEC) co-cultures. Increased plasma levels of NETs, tissue factor (TF) activity and sC5b-9 were detected in patients...
August 6, 2020: Journal of Clinical Investigation
https://read.qxmd.com/read/32723113/relevance-and-perspectives-of-the-use-of-chitosan-in-winemaking-a-review
#5
Antonio Castro Marín, Donato Colangelo, Milena Lambri, Claudio Riponi, Fabio Chinnici
Chitosan is a natural polymer that has quite recently been approved as an aid for microbial control, metal chelation, clarification, and reduction of contaminants in enology. In foods other than wine, chitosan has also been evidenced to have some other activities such as antioxidant and antiradical properties. Nevertheless, the actual extent of its activities in must and wines has not been fully established. This review aimed to gather and discuss the available scientific information on the efficacy of chitosan as a multifaceted aid in winemaking, including antimicrobial, chelating, clarifying and antioxidant activities, while summarizing the chemical mechanisms underlying its action...
July 29, 2020: Critical Reviews in Food Science and Nutrition
https://read.qxmd.com/read/32533108/author-correction-complement-as-a-target-in-covid-19
#6
Antonio M Risitano, Dimitrios C Mastellos, Markus Huber-Lang, Despina Yancopoulou, Cecilia Garlanda, Fabio Ciceri, John D Lambris
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
June 12, 2020: Nature Reviews. Immunology
https://read.qxmd.com/read/32511554/erythrocytes-reveal-complement-activation-in-patients-with-covid-19
#7
Lk Metthew Lam, Sophie J Murphy, Leticia Kuri-Cervantes, Ariel R Weisman, Caroline A G Ittner, John P Reilly, M Betina Pampena, Michael R Betts, E John Wherry, Wen-Chao Song, John D Lambris, Douglas B Cines, Nuala J Meyer, Nilam S Mangalmurti
COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multi-organ failure characterized by respiratory insufficiency, arrhythmias, thromboembolic complications and shock. The mortality of patients hospitalized with COVID-19 is unacceptably high and new strategies are urgently needed to rapidly identify and treat patients at risk for organ failure. Clinical epidemiologic studies demonstrate that vulnerability to organ failure is greatest after viral clearance from the upper airway, which suggests that dysregulation of the host immune response is a critical mediator of clinical deterioration and death...
May 22, 2020: medRxiv: the preprint server for health sciences
https://read.qxmd.com/read/32360516/the-first-case-of-covid-19-treated-with-the-complement-c3-inhibitor-amy-101
#8
Sara Mastaglio, Annalisa Ruggeri, Antonio M Risitano, Piera Angelillo, Despina Yancopoulou, Dimitrios C Mastellos, Markus Huber-Lang, Simona Piemontese, Andrea Assanelli, Cecilia Garlanda, John D Lambris, Fabio Ciceri
Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology. Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways. While a "cytokine storm" involving IL-6 and other cytokines has been documented, complement C3 activation has been implicated as an initial effector mechanism that exacerbates lung injury in preclinical models of SARS-CoV infection...
April 29, 2020: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://read.qxmd.com/read/32327719/complement-as-a-target-in-covid-19
#9
Antonio M Risitano, Dimitrios C Mastellos, Markus Huber-Lang, Despina Yancopoulou, Cecilia Garlanda, Fabio Ciceri, John D Lambris
No abstract text is available yet for this article.
April 23, 2020: Nature Reviews. Immunology
https://read.qxmd.com/read/32229292/prolonged-intraocular-residence-and-retinal-tissue-distribution-of-a-fourth-generation-compstatin-based-c3-inhibitor-in-non-human-primates
#10
Sarah Hughes, Justin Gumas, Rebecca Lee, Merita Romano, Nadja Berger, Avneesh Kumar Gautam, Georgia Sfyroera, Anna Lorena Chan, Gopalan Gnanaguru, Kip M Connor, Benjamin J Kim, Joshua L Dunaief, Daniel Ricklin, George Hajishengallis, Despina Yancopoulou, Edimara S Reis, Dimitrios C Mastellos, John D Lambris
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly population. Genetic studies in susceptible individuals have linked this ocular disease to deregulated complement activity that culminates in increased C3 turnover, retinal inflammation and photoreceptor loss. Therapeutic targeting of C3 has therefore emerged as a promising strategy for broadly intercepting the detrimental proinflammatory consequences of complement activation in the retinal tissue. In this regard, a PEGylated second-generation derivative of the compstatin family of C3-targeted inhibitors is currently in late-stage clinical development as a treatment option for geographic atrophy, an advanced form of AMD which lacks approved therapy...
March 27, 2020: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://read.qxmd.com/read/31819218/therapeutic-targeting-of-the-complement-system
#11
Daniel Ricklin, Dimitrios C Mastellos, John D Lambris
No abstract text is available yet for this article.
December 9, 2019: Nature Reviews. Drug Discovery
https://read.qxmd.com/read/31717543/changes-in-antioxidants-and-sensory-properties-of-italian-chocolates-and-related-ingredients-under-controlled-conditions-during-an-eighteen-month-storage-period
#12
Arianna Roda, Milena Lambri
BACKGROUND: While there has been an increasing interest in the health properties of chocolate, limited research has looked into the changes of antioxidants occurring in the time span from production to the best before date, which was a period of 18 months in this study. METHODS: Humidity, ash, pH, acidity, fiber, carotenoids, retinols, tocopherols, sugars, proteins, theobromine, caffeine, polyphenols, fats, the peroxide value, organic acids, and volatile compounds, along with the sensory profile, were monitored at 18-week intervals for 18 months under conditions simulating a factory warehouse or a point of sale...
November 9, 2019: Nutrients
https://read.qxmd.com/read/31605100/author-correction-stealth-corporate-innovation-an-emerging-threat-for-therapeutic-drug-development
#13
Dimitrios C Mastellos, Anna M Blom, E Sander Connolly, Mohamed R Daha, Brian V Geisbrecht, Berhane Ghebrehiwet, Piet Gros, George Hajishengallis, V Michael Holers, Markus Huber-Lang, Taroh Kinoshita, Tom E Mollnes, Robert A Montgomery, B Paul Morgan, Bo Nilsson, Ruben Pio, Daniel Ricklin, Antonio M Risitano, Ronald P Taylor, Alberto Mantovani, John P A Ioannidis, John D Lambris
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
October 11, 2019: Nature Immunology
https://read.qxmd.com/read/31562490/-stealth-corporate-innovation-an-emerging-threat-for-therapeutic-drug-development
#14
Dimitrios C Mastellos, Anna M Blom, E Sander Connolly, Mohamed R Daha, Brian V Geisbrecht, Berhane Ghebrehiwet, Piet Gros, George Hajishengallis, V Michael Holers, Markus Huber-Lang, Taroh Kinoshita, Tom E Mollnes, Robert A Montgomery, B Paul Morgan, Bo Nilsson, Ruben Pio, Daniel Ricklin, Antonio M Risitano, Ronald P Taylor, Alberto Mantovani, John P A Ioannidis, John D Lambris
No abstract text is available yet for this article.
September 27, 2019: Nature Immunology
https://read.qxmd.com/read/31542608/complement-activation-on-neutrophils-initiates-endothelial-adhesion-and-extravasation
#15
Antonina Akk, Luke E Springer, Lihua Yang, Samantha Hamilton-Burdess, John D Lambris, Huimin Yan, Ying Hu, Xiaobo Wu, Dennis E Hourcade, Mark J Miller, Christine T N Pham
Neutrophils are essential to the pathogenesis of many inflammatory diseases. In the autoantibody-mediated K/BxN model of inflammatory arthritis, the alternative pathway (AP) of complement and Fc gamma receptors (FcγRs) are required for disease development while the classical pathway is dispensable. The reason for this differential requirement is unknown. We show that within minutes of K/BxN serum injection complement activation (CA) is detected on circulating neutrophils, as evidenced by cell surface C3 fragment deposition...
October 2019: Molecular Immunology
https://read.qxmd.com/read/31514048/first-trials-to-assess-the-feasibility-of-grape-seed-powder-gsp-as-a-novel-and-sustainable-bentonite-alternative
#16
Elia Romanini, Jacqui M McRae, Donato Colangelo, Milena Lambri
Grape pathogenesis-related proteins can cause haze in wine that is undesirable for consumers. Bentonite is used to remove these proteins but is a non-renewable natural material and reduces wine volume due to poor settling. As a potential bentonite alternative, grape seeds powder (GSP) was added to four wines and two grape juice varieties. Addition to wine required high doses (25-32 g/L) for protein removal and haze prevention and this induced changes to wine composition. By contrast, addition to grape juice prior to fermentation required substantially lower doses of GSP (5 g/L) to prevent haze formation...
September 6, 2019: Food Chemistry
https://read.qxmd.com/read/31324874/clinical-promise-of-next-generation-complement-therapeutics
#17
REVIEW
Dimitrios C Mastellos, Daniel Ricklin, John D Lambris
The complement system plays a key role in pathogen immunosurveillance and tissue homeostasis. However, subversion of its tight regulatory control can fuel a vicious cycle of inflammatory damage that exacerbates pathology. The clinical merit of targeting the complement system has been established for rare clinical disorders such as paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome. Evidence from preclinical studies and human genome-wide analyses, supported by new molecular and structural insights, has revealed new pathomechanisms and unmet clinical needs that have thrust a new generation of complement inhibitors into clinical development for a variety of indications...
July 19, 2019: Nature Reviews. Drug Discovery
https://read.qxmd.com/read/31270150/cholesterol-crystals-induce-coagulation-activation-through-complement-dependent-expression-of-monocytic-tissue-factor
#18
Caroline S Gravastrand, Bjørg Steinkjer, Bente Halvorsen, Anne Landsem, Mona Skjelland, Eva Astrid Jacobsen, Trent M Woodruff, John D Lambris, Tom E Mollnes, Ole-Lars Brekke, Terje Espevik, Anne Mari A Rokstad
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 performed studies in lepirudin-based human whole blood and plasma models. In addition, immunohistological examinations of brain thrombi and vulnerable plaque material from patients with advanced carotid atherosclerosis were performed using polarization reflected light microscopy to identify CC...
July 3, 2019: Journal of Immunology
https://read.qxmd.com/read/31171642/complement-c3-inhibition-by-compstatin-cp40-prevents-intra-and-extravascular-hemolysis-of-red-blood-cells
#19
Inge Baas, Laura Delvasto-Nuñez, Peter Ligthart, Conny Brouwer, Claudia Folman, Edimara S Reis, Daniel Ricklin, John D Lambris, Diana Wouters, Masja de Haas, Ilse Jongerius, Sacha S Zeerleder
No abstract text is available yet for this article.
June 6, 2019: Haematologica
https://read.qxmd.com/read/31130967/corrigendum-targeting-complement-pathways-in-polytrauma-and-sepsis-induced-multiple-organ-dysfunction
#20
Ebru Karasu, Bo Nilsson, Jörg Köhl, John D Lambris, Markus Huber-Lang
[This corrects the article DOI: 10.3389/fimmu.2019.00543.].
2019: Frontiers in Immunology
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