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https://www.readbyqxmd.com/read/29648807/density-of-grafted-chains-in-thioglycerol-capped-cds-quantum-dots-determines-their-interaction-with-aluminum-iii-in-water
#1
Nassim Ben Brahim, Mélanie Poggi, Jean-Christophe Lambry, Naim Bel Haj Mohamed, Rafik Ben Chaâbane, Michel Negrerie
We aimed to quantify the interaction of water-soluble-functionalized CdS quantum dots (QDs) with metal cations from their composition and physical properties. From the diameter of thioglycerol-capped nanoparticles (TG-CdS QDs) measured by electronic microscopy ( D = 12.3 ± 0.3 nm), we calculated the molecular mass of the individual particle MAQD = (3 ± 0.5) × 106 g·mol-1 and its molar absorption coefficient ε450 = 21 × 106 M-1 ·cm-1 . We built a three-dimensional model of the TG-CdS QDs in agreement with the structural data, which allowed us to quantify the number of thioglycerol grafted chains to ∼2000 per QD...
April 12, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29507356/innate-immune-responses-to-trauma
#2
REVIEW
Markus Huber-Lang, John D Lambris, Peter A Ward
Trauma can affect any individual at any location and at any time over a lifespan. The disruption of macrobarriers and microbarriers induces instant activation of innate immunity. The subsequent complex response, designed to limit further damage and induce healing, also represents a major driver of complications and fatal outcome after injury. This Review aims to provide basic concepts about the posttraumatic response and is focused on the interactive events of innate immunity at frequent sites of injury: the endothelium at large, and sites within the lungs, inside and outside the brain and at the gut barrier...
April 2018: Nature Immunology
https://www.readbyqxmd.com/read/29497373/the-complement-system-is-critical-in-maintaining-retinal-integrity-during-aging
#3
Ryo Mukai, Yoko Okunuki, Deeba Husain, Clifford B Kim, John D Lambris, Kip M Connor
The complement system is a key component of innate immunity comprised of soluble components that form a proteolytic cascade leading to the generation of effector molecules involved in cellular clearance. This system is highly activated not only under general inflammatory conditions such as infections, collagen diseases, nephritis, and liver diseases, but also in focal ocular diseases. However, little is known about the role of the complement system in retinal homeostasis during aging. Using young (6-week-old) and adult (6-month-old) mice in wild type (C57BL/6) and complement knockout strains ( C1q -/- , Mbl a/c -/- , Fb -/- , C3 -/- , and C5 -/- ), we compared amplitudes of electroretinograms (ERG) and thicknesses of retinal layers in spectral domain optical coherence tomography between young and adult mice...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29461464/protective-effects-of-the-complement-inhibitor-compstatin-cp40-in-hemorrhagic-shock
#4
Martijn van Griensven, Daniel Ricklin, Stephanie Denk, Rebecca Halbgebauer, Christian K Braun, Anke Schultze, Felix Hönes, Sofia Koutsogiannaki, Alexandra Primikyri, Edimara Reis, David Messerer, Sebastian Hafner, Peter Radermacher, Ali-Reza Biglarnia, Ranillo R G Resuello, Joel V Tuplano, Benjamin Mayer, Kristina Nilsson, Bo Nilsson, John D Lambris, Markus Huber-Lang
Trauma-induced hemorrhagic shock (HS) plays a decisive role in the development of immune, coagulation, and organ dysfunction often resulting in a poor clinical outcome. Imbalanced complement activation is intricately associated with the molecular danger response and organ damage after HS. Thus, inhibition of the central complement component C3 as turnstile of both inflammation and coagulation is hypothesized as a rational strategy to improve the clinical course after HS.Applying intensive care conditions, anaesthetized, monitored, and protectively ventilated non-human primates (NHP; cynomolgus monkeys) received a pressure-controlled severe HS (60 min at MAP 30 mmHg) with subsequent volume resuscitation...
February 14, 2018: Shock
https://www.readbyqxmd.com/read/29218045/factor-h-c-terminal-domains-are-critical-for-regulation-of-platelet-granulocyte-aggregate-formation
#5
Adam Z Blatt, Gurpanna Saggu, Claudio Cortes, Andrew P Herbert, David Kavanagh, Daniel Ricklin, John D Lambris, Viviana P Ferreira
Platelet/granulocyte aggregates (PGAs) increase thromboinflammation in the vasculature, and PGA formation is tightly controlled by the complement alternative pathway (AP) negative regulator, Factor H (FH). Mutations in FH are associated with the prothrombotic disease atypical hemolytic uremic syndrome (aHUS), yet it is unknown whether increased PGA formation contributes to the thrombosis seen in patients with aHUS. Here, flow cytometry assays were used to evaluate the effects of aHUS-related mutations on FH regulation of PGA formation and characterize the mechanism...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29199277/the-renaissance-of-complement-therapeutics
#6
REVIEW
Daniel Ricklin, Dimitrios C Mastellos, Edimara S Reis, John D Lambris
The increasing number of clinical conditions that involve a pathological contribution from the complement system - many of which affect the kidneys - has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development...
January 2018: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29144501/novel-mechanisms-and-functions-of-complement
#7
REVIEW
George Hajishengallis, Edimara S Reis, Dimitrios C Mastellos, Daniel Ricklin, John D Lambris
Progress at the beginning of the 21st century transformed the perception of complement from that of a blood-based antimicrobial system to that of a global regulator of immunity and tissue homeostasis. More recent years have witnessed remarkable advances in structure-function insights and understanding of the mechanisms and locations of complement activation, which have added new layers of complexity to the biology of complement. This complexity is readily reflected by the multifaceted and contextual involvement of complement-driven networks in a wide range of inflammatory and neurodegenerative disorders and cancer...
November 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/29118090/complement-activation-via-a-c3a-receptor-pathway-alters-cd4-t-lymphocytes-and-mediates-lung-cancer-progression
#8
Jeff W Kwak, Jennifer Laskowski, Howard Y Li, Maria V McSharry, Trisha R Sippel, Bonnie L Bullock, Amber M Johnson, Joanna M Poczobutt, Alexander J Neuwelt, Stephen P Malkoski, Mary C Weiser-Evans, John D Lambris, Eric T Clambey, Joshua M Thurman, Raphael A Nemenoff
The complement cascade is a part of the innate immune system that acts primarily to remove pathogens and injured cells. However, complement activation is also peculiarly associated with tumor progression. Here we report mechanistic insights into this association in multiple immunocompetent orthotopic models of lung cancer. After tumor engraftment, we observed systemic activation of the complement cascade as reflected by elevated levels of the key regulator C3a. Notably, growth of primary tumors and metastases was both strongly inhibited in C3-deficient mice (C3-/- mice), with tumors undetectable in many subjects...
January 1, 2018: Cancer Research
https://www.readbyqxmd.com/read/29070810/complement-receptors-c5ar1-and-c5ar2-act-differentially-during-the-early-immune-response-after-bone-fracture-but-are-similarly-involved-in-bone-repair
#9
Anna Kovtun, Stephanie Bergdolt, Yvonne Hägele, Rebekka Matthes, John D Lambris, Markus Huber-Lang, Anita Ignatius
Severely injured patients frequently suffer compromised fracture healing because of systemic post-traumatic inflammation. An important trigger of the posttraumatic immune response is the complement anaphylatoxin C5a, which acts via two receptors, C5aR1 and C5aR2, expressed on immune and bone cells. The blockade of C5a-mediated inflammation during the early inflammatory phase was demonstrated to improve fracture healing after severe injury. However, the distinct roles of the two complement receptors C5aR1 and C5aR2 in bone has to date not been studied...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28973891/complement-activation-fragment-c4a-mediates-effector-functions-by-binding-as-untethered-agonist-to-protease-activated-receptors-1-and-4
#10
HongBin Wang, Daniel Ricklin, John D Lambris
C4a is a small protein released from complement component C4 upon activation of the complement system's classical and lectin pathways, which are important constituents of innate immune surveillance. Despite the structural similarity between C4a and well-described anaphylatoxins C3a and C5a, the binding partner and biological function of C4a have remained elusive. Using a cell-based reporter assay, we screened C4a against a panel of both known and orphan G protein-coupled receptors and now provide evidence that C4a is a ligand for protease-activated receptor (PAR)1 and PAR4...
October 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28941899/oxygen-availability-and-strain-combination-modulate-yeast-growth-dynamics-in-mixed-culture-fermentations-of-grape-must-with-starmerella-bacillaris-and-saccharomyces-cerevisiae
#11
Vasileios Englezos, Francesco Cravero, Fabrizio Torchio, Kalliopi Rantsiou, Anne Ortiz-Julien, Milena Lambri, Vincenzo Gerbi, Luca Rolle, Luca Cocolin
Starmerella bacillaris (synonym Candida zemplinina) is a non-Saccharomyces yeast that has been proposed as a co-inoculant of selected Saccharomyces cerevisiae strains in mixed culture fermentations to enhance the analytical composition of the wines. In order to acquire further knowledge on the metabolic interactions between these two species, in this study we investigated the impact of oxygen addition and combination of Starm. bacillaris with S. cerevisiae strains on the microbial growth and metabolite production...
February 2018: Food Microbiology
https://www.readbyqxmd.com/read/28932632/local-endothelial-complement-activation-reverses-endothelial-quiescence-enabling-t-cell-homing-and-tumor-control-during-t-cell-immunotherapy
#12
Andrea Facciabene, Francesco De Sanctis, Stefano Pierini, Edimara S Reis, Klara Balint, John Facciponte, Jens Rueter, Masahiro Kagabu, Paola Magotti, Evripidis Lanitis, Robert A DeAngelis, Ronald J Buckanovich, Wenchao C Song, John D Lambris, George Coukos
Cancer immunotherapy relies upon the ability of T cells to infiltrate tumors. The endothelium constitutes a barrier between the tumor and effector T cells, and the ability to manipulate local vascular permeability could be translated into effective immunotherapy. Here, we show that in the context of adoptive T cell therapy, antitumor T cells, delivered at high enough doses, can overcome the endothelial barrier and infiltrate tumors, a process that requires local production of C3, complement activation on tumor endothelium and release of C5a...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920587/complement-in-cancer-untangling-an-intricate-relationship
#13
REVIEW
Edimara S Reis, Dimitrios C Mastellos, Daniel Ricklin, Alberto Mantovani, John D Lambris
In tumour immunology, complement has traditionally been considered as an adjunctive component that enhances the cytolytic effects of antibody-based immunotherapies, such as rituximab. Remarkably, research in the past decade has uncovered novel molecular mechanisms linking imbalanced complement activation in the tumour microenvironment with inflammation and suppression of antitumour immune responses. These findings have prompted new interest in manipulating the complement system for cancer therapy. This Review summarizes our current understanding of complement-mediated effector functions in the tumour microenvironment, focusing on how complement activation can act as a negative or positive regulator of tumorigenesis...
January 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28879212/safety-and-efficacy-of-the-complement-inhibitor-amy-101-in-a-natural-model-of-periodontitis-in-non-human-primates
#14
Tetsuhiro Kajikawa, Ruel A Briones, Ranillo R G Resuello, Joel V Tuplano, Edimara S Reis, Evlambia Hajishengallis, Cristina A G Garcia, Despina Yancopoulou, John D Lambris, George Hajishengallis
Periodontitis is a chronic inflammatory disease associated with overactivation of the complement system. Recent preclinical studies suggest that host-modulation therapies may contribute to effective treatment of human periodontitis, which may lead to loss of teeth and function if untreated. We previously showed that locally administered AMY-101 (Cp40), a peptidic inhibitor of the central complement component C3, can inhibit naturally occurring periodontitis in non-human primates (NHPs) when given once a week...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28759066/structural-changes-and-picosecond-to-second-dynamics-of-cytochrome-c-in-interaction-with-nitric-oxide-in-ferrous-and-ferric-redox-states
#15
Sergei G Kruglik, Byung-Kuk Yoo, Jean-Christophe Lambry, Jean-Louis Martin, Michel Negrerie
Apart from its role in electron transfer, mitochondrial cytochrome c also plays a role in apoptosis and is subject to nitrosylation. The cleavage of the Fe-Met80 bond plays a role in several processes including the release of Cyt c from mitochondria or increase of its peroxidase activity. Nitrosylation of Cyt c precludes the reformation of the disrupted Fe-Met80 bond and was shown to occur during apoptosis. These physiological properties are associated with a conformational change of the heme center of Cyt c...
August 16, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28748042/porphyromonas-gingivalis-disturbs-host-commensal-homeostasis-by-changing-complement-function
#16
REVIEW
Ingar Olsen, John D Lambris, George Hajishengallis
Porphyromonas gingivalis is a Gram-negative anaerobic rod that has been proposed as an orchestrator of complement-dependent dysbiotic inflammation. This notion was suggested from its capacities to manipulate the complement-Toll-like receptor crosstalk in ways that promote dysbiosis and periodontal disease in animal models. Specifically, while at low colonization levels, P. gingivalis interferes with innate immunity and leads to changes in the counts and composition of the oral commensal microbiota. The resulting dysbiotic microbial community causes disruption of host-microbial homeostasis, leading to inflammatory bone loss...
2017: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/28671713/complement-c5a-induced-changes-in-neutrophil-morphology-during-inflammation
#17
S Denk, R P Taylor, R Wiegner, E M Cook, M A Lindorfer, K Pfeiffer, S Paschke, T Eiseler, M Weiss, E Barth, J D Lambris, M Kalbitz, T Martin, H Barth, D A C Messerer, F Gebhard, M S Huber-Lang
The complement and neutrophil defence systems, as major components of innate immunity, are activated during inflammation and infection. For neutrophil migration to the inflamed region, we hypothesized that the complement activation product C5a induces significant changes in cellular morphology before chemotaxis. Exposure of human neutrophils to C5a dose- and time-dependently resulted in a rapid C5a receptor-1 (C5aR1)-dependent shape change, indicated by enhanced flow cytometric forward-scatter area values. Similar changes were observed after incubation with zymosan-activated serum and in blood neutrophils during murine sepsis, but not in mice lacking the C5aR1...
September 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28671664/regulator-dependent-mechanisms-of-c3b-processing-by-factor-i-allow-differentiation-of-immune-responses
#18
Xiaoguang Xue, Jin Wu, Daniel Ricklin, Federico Forneris, Patrizia Di Crescenzio, Christoph Q Schmidt, Joke Granneman, Thomas H Sharp, John D Lambris, Piet Gros
The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of C3b remains unclear. We present a crystal structure of C3b in complex with FI and regulator factor H (FH; domains 1-4 with 19-20). FI binds C3b-FH between FH domains 2 and 3 and a reoriented C3b C-terminal domain and docks onto the first scissile bond, while stabilizing its catalytic domain for proteolytic activity...
August 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28579778/iron-oxide-nanoparticles-induce-cytokine-secretion-in-a-complement-dependent-manner-in-a-human-whole-blood-model
#19
Susann Wolf-Grosse, Anne Mari Rokstad, Syed Ali, John D Lambris, Tom E Mollnes, Asbjørn M Nilsen, Jørgen Stenvik
Iron oxide nanoparticles (IONPs) are promising nanomaterials for biomedical applications. However, their inflammatory potential has not been fully established. Here, we used a lepirudin anti-coagulated human whole blood model to evaluate the potential of 10 nm IONPs to activate the complement system and induce cytokine production. Reactive oxygen species and cell death were also assessed. The IONPs activated complement, as measured by C3a, C5a and sC5b-9, and induced the production of pro-inflammatory cytokines in a particle-dose dependent manner, with the strongest response at 10 µg/mL IONPs...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28576714/alginate-microbeads-are-coagulation-compatible-while-alginate-microcapsules-activate-coagulation-secondary-to-complement-or-directly-through-fxii
#20
Caroline Gravastrand, Shamal Hamad, Hilde Fure, Bjørg Steinkjer, Liv Ryan, Josè Oberholzer, John D Lambris, Igor Lacík, Tom Eirik Mollnes, Terje Espevik, Ole-Lars Brekke, Anne Mari Rokstad
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 strategies. We used a lepirudin based human whole blood model to investigate the coagulation potentials of alginate-based microspheres: alginate microbeads (Ca/Ba Beads), alginate poly-l-lysine microcapsules (APA and AP microcapsules) and sodium alginate-sodium cellulose sulfate-poly(methylene-co-cyanoguanidine) microcapsules (PMCG microcapsules)...
August 2017: Acta Biomaterialia
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