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neutrophil substrate

Joseph A Caruso, Mylinh T Duong, Jason P W Carey, Kelly K Hunt, Khandan Keyomarsi
Cyclin E, a regulatory subunit of cyclin-dependent kinase 2 (CDK2), is central to the initiation of DNA replication at the G1 /S checkpoint. Tight temporal control of cyclin E is essential to the coordination of cell-cycle processes and the maintenance of genome integrity. Overexpression of cyclin E in human tumors was first observed in the 1990s and led to the identification of oncogenic roles for deregulated cyclin E in experimental models. A decade later, low-molecular-weight cyclin E (LMW-E) isoforms were observed in aggressive tumor subtypes...
September 7, 2018: Cancer Research
Prasad Dasari, Iordana A Shopova, Maria Stroe, Dirk Wartenberg, Hans Martin-Dahse, Niklas Beyersdorf, Peter Hortschansky, Stefanie Dietrich, Zoltán Cseresnyés, Marc Thilo Figge, Martin Westermann, Christine Skerka, Axel A Brakhage, Peter F Zipfel
The opportunistic fungal pathogen Aspergillus fumigatus can cause life-threatening infections, particularly in immunocompromised patients. Most pathogenic microbes control host innate immune responses at the earliest time, already before infiltrating host immune cells arrive at the site of infection. Here, we identify Aspf2 as the first A. fumigatus Factor H-binding protein. Aspf2 recruits several human plasma regulators, Factor H, factor-H-like protein 1 (FHL-1), FHR1, and plasminogen. Factor H contacts Aspf2 via two regions located in SCRs6-7 and SCR20...
2018: Frontiers in Immunology
Elena A Nicu, Patrick Rijkschroeff, Eva Wartewig, Kamran Nazmi, Bruno G Loos
BACKGROUND: Maintaining oral health is a continuous and dynamic process that also involves the immune system. Polymorphonuclear neutrophils (PMNs) migrate from blood circulation and become apparent in the oral fluid. Controversies exist regarding the specific role of the oral PMNs (oPMNs) in the presence of chronic oral inflammation, such as periodontitis. In this study we characterized cell counts, activation status, apoptosis, and reactive oxygen species (ROS) generation by oPMNs and circulatory (cPMNs), and the salivary protease activity, in subjects with and without periodontitis...
August 24, 2018: BMC Oral Health
Anne-Sophie Archambault, Caroline Turcotte, Cyril Martin, Véronique Provost, Marie-Chantal Larose, Catherine Laprise, Jamila Chakir, Élyse Bissonnette, Michel Laviolette, Ynuk Bossé, Nicolas Flamand
Neutrophils and eosinophils are important sources of bioactive lipids from the 5- and the 15-lipoxygenase (LO) pathways. Herein, we compared the effectiveness of humans eosinophils and eosinophil-depleted neutrophils to synthesize 15-LO metabolites using a cocktail of different 15-LO substrates as well as their sensitivities to eight documented 15-lipoxygenase inhibitors. The treatment of neutrophils and eosinophils with linoleic acid, dihomo-γ-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid and arachidonyl-ethanolamide, led to the synthesis of 13-HODE, 15-HETrE, 15-HETE, 15-HEPE, 14-HDHA/17-HDHA, and 15-hydroxy-AEA...
2018: PloS One
Rose L Szabady, Christopher Louissaint, Anneke Lubben, Bailu Xie, Shaun Reeksting, Christine Tuohy, Zachary Demma, Sage E Foley, Christina S Faherty, Alejandro Llanos-Chea, Andrew J Olive, Randall J Mrsny, Beth A McCormick
Neutrophil influx into the intestinal lumen is a critical response to infectious agents, but is also associated with severe intestinal damage observed in idiopathic inflammatory bowel disease. The chemoattractant hepoxilin A3, an eicosanoid secreted from intestinal epithelial cells by the apically restricted efflux pump multidrug resistance protein 2 (MRP2), mediates this neutrophil influx. Information about a possible counterbalance pathway that could signal the lack of or resolution of an apical inflammatory signal, however, has yet to be described...
August 31, 2018: Journal of Clinical Investigation
Linda A Stevens, Joel Moss
Methods are described for determination of arginine-specific mono-ADP-ribosyltransferase activity of purified proteins and intact cells by monitoring the transfer of ADP-ribose from NAD+ to a model substrate, e.g., arginine, agmatine, and peptide (human neutrophil peptide-1 [HNP1]), and for the nonenzymatic hydrolysis of ADP-ribose-arginine to ornithine, a noncoded amino acid. In addition, preparation of purified ADP-ribosylarginine is included as a control substrate for ADP-ribosylation reactions.
2018: Methods in Molecular Biology
Marcello Monti, Viviana De Rosa, Francesca Iommelli, Maria Vincenza Carriero, Cristina Terlizzi, Rosa Camerlingo, Stefania Belli, Rosa Fonti, Giovanni Di Minno, Silvana Del Vecchio
Neutrophil extracellular traps (NETs), in addition to their function as a host defense mechanism, play a relevant role in thrombus formation and metastatic dissemination of cancer cells. Here we screened different cancer cell lines endogenously expressing a variety of integrins for their ability to bind to NETs. To this end, we used NETs isolated from neutrophil-like cells as a substrate for adhesion assays of HT1080, U-87 MG, H1975, DU 145, PC-3 and A-431 cells. Levels of α5, αIIb, αv, β1, β3 and β5 chains were determined by western blot analysis in all cell lines and levels of whole integrins on the plasma membrane were assessed by fluorescence-activated cell sorting (FACS) analysis...
August 9, 2018: International Journal of Molecular Sciences
Natacha Jugniot, Indranil Duttagupta, Angélique Rivot, Philippe Massot, Colleen Cardiet, Anne Pizzoccaro, Marion Jean, Nicolas Vanthuyne, Jean-Michel Franconi, Pierre Voisin, Gilles Devouassoux, Elodie Parzy, Eric Thiaudiere, Sylvain R A Marque, Abderrazzak Bentaher, Gérard Audran, Philippe Mellet
Pulmonary inflammatory diseases are a major burden worldwide. They have in common an influx of neutrophils. Neutrophils secrete unchecked proteases at inflammation sites consequently leading to a protease/inhibitor imbalance. Among these proteases, neutrophil elastase is responsible for the degradation of the lung structure via elastin fragmentation. Therefore, monitoring the protease/inhibitor status in lungs non-invasively would be an important diagnostic tool. Herein we present the synthesis of a MeO-Suc-(Ala)2 -Pro-Val-nitroxide, a line-shifting elastase activity probe suitable for Electron Paramagnetic Resonance spectroscopy (EPR) and Overhauser-enhanced Magnetic Resonance Imaging (OMRI)...
August 6, 2018: Free Radical Biology & Medicine
Luca Liberale, Maria Bertolotto, Federico Carbone, Paola Contini, Patricia Wüst, Giovanni Spinella, Bianca Pane, Domenico Palombo, Aldo Bonaventura, Aldo Pende, François Mach, Franco Dallegri, Giovanni G Camici, Fabrizio Montecucco
BACKGROUND: Neutrophil functions have been shown to be modulated by adipocytokines during atherogenesis. The immuno-regulatory role of resistin on neutrophil-mediated activities in atherosclerotic patients remains elusive. Here, we aimed at exploring the association between serum levels of resistin and neutrophil products either in the systemic circulation or within plaques in a cohort of patients with severe carotid plaque stenosis undergoing endarterectomy. In addition, we assessed the effects of resistin on neutrophil pro-atherosclerotic functions in vitro...
July 24, 2018: International Journal of Cardiology
Janina Eisenbeis, Mona Saffarzadeh, Henrik Peisker, Philipp Jung, Nicolas Thewes, Klaus T Preissner, Mathias Herrmann, Virginie Molle, Brian V Geisbrecht, Karin Jacobs, Markus Bischoff
The extracellular adherence protein (Eap) of Staphylococcus aureus is a secreted protein known to exert a number of adhesive and immunomodulatory properties. Here we describe the intrinsic DNA binding activity of this multifunctional secretory factor. By using atomic force microscopy, we provide evidence that Eap can bind and aggregate DNA. While the origin of the DNA substrate (e.g., eukaryotic, bacterial, phage, and artificial DNA) seems to not be of major importance, the DNA structure (e.g., linear or circular) plays a critical role with respect to the ability of Eap to bind and condense DNA...
2018: Frontiers in Cellular and Infection Microbiology
J Vincent Edwards, Krystal R Fontenot, Falk Liebner, Brian D Condon
The growing incidence of chronic wounds in the world population has prompted increased interest in chronic wound dressings with protease-modulating activity and protease point of care sensors to treat and enable monitoring of elevated protease-based wound pathology. However, the overall design features needed for the combination of a chronic wound dressing that lowers protease activity along with protease detection capability as a single platform for semi-occlusive dressings has scarcely been addressed. The interface of dressing and sensor specific properties (porosity, permeability, moisture uptake properties, specific surface area, surface charge, and detection) relative to sensor bioactivity and protease sequestrant performance is explored here...
July 18, 2018: Sensors
P Nyssen, A Mouithys-Mickalad, G Minguet, E Sauvage, J Wouters, T Franck, M Hoebeke
Morphine is an opioid alkaloid commonly used in clinical practice for its analgesic properties. The phenolic hydroxyl group of that phenanthrene derivative is pivotal for binding to opioid receptors but it may also be responsible for the antioxidant behavior of morphine reported in several in vitro experiments. In this study, we assessed the effect of morphine on myeloperoxidase (MPO), a hemic enzyme from azurophilic granules of polymorphonuclear neutrophils involved in the production of cytotoxic and microbicidal reactive oxidants during inflammatory response...
July 10, 2018: Biochimica et Biophysica Acta
Shiliang Feng, Lüwen Zhou, Yan Zhang, Shouqin Lü, Mian Long
Directional neutrophil migration during human immune responses is a highly coordinated process regulated by both biochemical and biomechanical environments. In this paper, we developed an integrative mathematical model of neutrophil migration using a lattice Boltzmann-particle method built in-house to solve the moving boundary problem with spatiotemporal regulation of biochemical components. The mechanical features of the cell cortex are modeled by a series of spring-connected nodes representing discrete cell-substrate adhesive sites...
July 2, 2018: Biomechanics and Modeling in Mechanobiology
Rao Fu, Soichiro Tajima, Kimitaka Suetsugu, Hiroyuki Watanabe, Nobuaki Egashira, Satohiro Masuda
Calcineurin inhibitors (CNIs), such as cyclosporine A and tacrolimus, are widely used immunosuppressive agents for the prevention of post-transplantation rejection and have improved 1-year graft survival rates by up to 90%. However, CNIs can induce severe reactions, such as acute or chronic allograft nephropathy, hypertension, and neurotoxicity. Because CNIs have varied bioavailabilities, narrow therapeutic ranges, and individual propensities for toxic effects, therapeutic drug monitoring is necessary for all CNIs...
June 27, 2018: Acta Pharmacologica Sinica
Mieke Gouwy, Mieke De Buck, Sara Abouelasrar Salama, Jennifer Vandooren, Sofie Knoops, Noëmie Pörtner, Lotte Vanbrabant, Nele Berghmans, Ghislain Opdenakker, Paul Proost, Jo Van Damme, Sofie Struyf
Serum amyloid A1 (SAA1) is a prototypic acute phase protein, induced to extremely high levels by physical insults, including inflammation and infection. Human SAA and its NH2 -terminal part have been studied extensively in the context of amyloidosis. By contrast, little is known about COOH-terminal fragments of SAA. Intact SAA1 chemoattracts leukocytes via the G protein-coupled receptor formyl peptide receptor like 1/formyl peptide receptor 2 (FPR2). In addition to direct leukocyte activation, SAA1 induces chemokine production by signaling through toll-like receptor 2...
2018: Frontiers in Immunology
Jingjing Tang, Jeremy M Frey, Carole L Wilson, Angela Moncada-Pazos, Clémence Levet, Matthew Freeman, Michael E Rosenfeld, E Richard Stanley, Elaine W Raines, Karin E Bornfeldt
Macrophages are prominent cells in acute and chronic inflammatory diseases. Recent studies highlight a role for macrophage proliferation post monocyte recruitment in inflammatory conditions. Using an acute peritonitis model, we identify a significant defect in macrophage proliferation in mice lacking leukocyte transmembrane protease ADAM17. The defect is associated with decreased levels of macrophage colony-stimulating factor-1 (CSF-1) in the peritoneum, and is rescued by intraperitoneal injection of CSF-1...
June 11, 2018: Molecular and Cellular Biology
L L K Leung, J Morser
Two basic carboxypeptidases, carboxypeptidase B2 (CPB2) and carboxypeptidase N (CPN) are present in plasma. CPN is constitutively active, whereas CPB2 circulates as a precursor, procarboxypeptidase B2 (proCPB2), that needs to be activated by the thrombin-thrombomodulin complex or plasmin bound to glycosaminoglycans. The substrate specificities of CPB2 and CPN are similar; they both remove C-terminal basic amino acids from bioactive peptides and proteins, thereby inactivating them. The complement cascade is a cascade of proteases and cofactors activated by pathogens or dead cells, divided into two phases, with the second phase only being triggered if sufficient C3b is present...
June 8, 2018: Journal of Thrombosis and Haemostasis: JTH
Mona H C Biermann, Sebastian Boeltz, Elmar Pieterse, Jasmin Knopf, Jürgen Rech, Rostyslav Bilyy, Johan van der Vlag, Angela Tincani, Jörg H W Distler, Gerhard Krönke, Georg Andreas Schett, Martin Herrmann, Luis E Muñoz
Deficient clearance of apoptotic cells reportedly contributes to the etiopathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Based on this knowledge, we developed a highly specific and sensitive test for the detection of SLE autoantibodies (AAb) utilizing secondary NEcrotic cell (SNEC)-derived material as a substrate. The goal of the present study was to validate the use of SNEC as an appropriate antigen for the diagnosis of SLE in large cohort of patients. We confirmed the presence of apoptotically modified autoantigens on SNEC (dsDNA, high mobility group box 1 protein, apoptosis-associated chromatin modifications, e...
2018: Frontiers in Immunology
Päivi Sirniö, Anne Tuomisto, Taina Tervahartiala, Timo Sorsa, Kai Klintrup, Toni Karhu, Karl-Heinz Herzig, Jyrki Mäkelä, Tuomo J Karttunen, Tuula Salo, Markus J Mäkinen, Juha P Väyrynen
BACKGROUND: Matrix metalloproteinase-8 (MMP-8) is a protease mainly expressed by neutrophils that cleaves numerous substrates, including collagens and cytokines. We have previously shown that serum MMP-8 levels increase in colorectal cancer (CRC) and correlate with distant metastasis. However, short follow-up in our prospective cohort did not enable survival analyses at the time of the first publication. METHODS: Preoperative serum MMP-8 levels were measured by immunofluorometric assay in 271 CRC patients and related to clinicopathological parameters, markers of systemic inflammation (modified Glasgow Prognostic Score, mGPS; serum levels of C-reactive protein (CRP), albumin and 13 cytokines), the density of six types of tumour-infiltrating immune cells and survival...
July 2018: British Journal of Cancer
Dimitry Y Sorokin, Alexander Y Merkel, Ben Abbas, Kira S Makarova, W Irene C Rijpstra, M Koenen, Jaap S Sinninghe Damsté, Erwin A Galinski, Eugene V Koonin, Mark C M van Loosdrecht
Methanogenic enrichments from hypersaline lakes at moderate thermophilic conditions have resulted in the cultivation of an unknown deep lineage of euryarchaeota related to the class Halobacteria. Eleven soda lake isolates and three salt lake enrichment cultures were methyl-reducing methanogens that utilize C1 methylated compounds as electron acceptors and H2 or formate as electron donors, but they were unable to grow on either substrates alone or to form methane from acetate. They are extreme halophiles, growing optimally at 4 M total Na+ and the first representatives of methanogens employing the 'salt-in' osmoprotective mechanism...
July 2018: International Journal of Systematic and Evolutionary Microbiology
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