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https://www.readbyqxmd.com/read/28096297/frontline-science-tumor-necrosis-factor-%C3%AE-stimulation-and-priming-of-human-neutrophil-granule-exocytosis
#1
Kenneth R McLeish, Michael L Merchant, T Michael Creed, Shweta Tandon, Michelle T Barati, Silvia M Uriarte, Richard A Ward
Neutrophil granule exocytosis plays an important role in innate and adaptive immune responses. The present study examined TNF-α stimulation or priming of exocytosis of the 4 neutrophil granule subsets. TNF-α stimulated exocytosis of secretory vesicles and gelatinase granules and primed specific and azurophilic granule exocytosis to fMLF stimulation. Both stimulation and priming of exocytosis by TNF-α were dependent on p38 MAPK activity. Bioinformatic analysis of 1115 neutrophil proteins identified by mass spectrometry as being phosphorylated by TNF-α exposure found that actin cytoskeleton regulation was a major biologic function...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28053237/highly-selective-cleavage-of-cytokines-and-chemokines-by-the-human-mast-cell-chymase-and-neutrophil-cathepsin-g
#2
Zhirong Fu, Michael Thorpe, Rahel Alemayehu, Ananya Roy, Jukka Kervinen, Lawrence de Garavilla, Magnus Åbrink, Lars Hellman
Human mast cell chymase (HC) and human neutrophil cathepsin G (hCG) show relatively similar cleavage specificities: they both have chymotryptic activity but can also cleave efficiently after leucine. Their relatively broad specificity suggests that they may cleave almost any substrate if present in high enough concentrations or for a sufficiently long time. A number of potential substrates have been identified for these enzymes and, recently, these enzymes have also been implicated in regulating cytokine activity by cleaving numerous cytokines and chemokines...
January 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28045523/design-of-potent-and-selective-cathepsin-g-inhibitors-based-on-the-sunflower-trypsin-inhibitor-1-scaffold
#3
Joakim E Swedberg, Choi Yi Li, Simon J de Veer, Conan K Wang, David J Craik
Neutrophils are directly responsible for destroying invading pathogens via reactive oxygen species, antimicrobial peptides, and neutrophil serine proteases (NSPs). Imbalance between NSP activity and endogenous protease inhibitors is associated with chronic inflammatory disorders, and engineered inhibitors of NSPs are a potential therapeutic pathway. In this study we characterized the extended substrate specificity (P4-P1) of the NSP cathepsin G using a peptide substrate library. Substituting preferred cathepsin G substrate sequences into sunflower trypsin inhibitor-1 (SFTI-1) produced a potent cathepsin G inhibitor (Ki = 0...
January 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27993028/nanocontact-printing-of-proteins-on-physiologically-soft-substrates-to-study-cell-haptotaxis
#4
Donald MacNearney, Bernard Mak, Grant Ongo, Timothy E Kennedy, David Juncker
Surface bound guidance cues and gradients are vital for directing cellular processes during development and repair. In vivo, these cues are often presented within a soft extracellular matrix with elastic moduli E < 10 kPa, but in vitro haptotaxis experiments have been conducted primarily on hard substrates with elastic moduli in the MPa to GPa range. Here, a technique is presented for patterning haptotactic proteins with nanometer resolution on soft substrates with physiological elasticity. A new nanocontact printing process was developed that circumvented the use of plasma activation that was found to alter the mechanical properties of the substrate...
December 20, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/27992534/the-pig-a-relevant-model-for-evaluating-the-neutrophil-serine-protease-activities-during-acute-pseudomonas-aeruginosa-lung-infection
#5
Claire Chevaleyre, Mickaël Riou, Déborah Bréa, Clarisse Vandebrouck, Céline Barc, Jérémy Pezant, Sandrine Melo, Michel Olivier, Rémy Delaunay, Olivier Boulesteix, Patricia Berthon, Christelle Rossignol, Julien Burlaud Gaillard, Frédéric Becq, Francis Gauthier, Mustapha Si-Tahar, François Meurens, Mustapha Berri, Ignacio Caballero-Posadas, Sylvie Attucci
The main features of lung infection and inflammation are a massive recruitment of neutrophils and the subsequent release of neutrophil serine proteases (NSPs). Anti-infectious and/or anti-inflammatory treatments must be tested on a suitable animal model. Mice models do not replicate several aspects of human lung disease. This is particularly true for cystic fibrosis (CF), which has led the scientific community to a search for new animal models. We have shown that mice are not appropriate for characterizing drugs targeting neutrophil-dependent inflammation and that pig neutrophils and their NSPs are similar to their human homologues...
2016: PloS One
https://www.readbyqxmd.com/read/27939504/anti-inflammatory-effects-on-ischemia-reperfusion-injured-lung-transplants-by-the-cluster-of-differentiation-26-dipeptidylpeptidase-4-cd26-dpp4-inhibitor-vildagliptin
#6
Jae-Hwi Jang, Yoshito Yamada, Florian Janker, Ingrid De Meester, Lesley Baerts, Gwendolyn Vliegen, Ilhan Inci, Shampa Chatterjee, Walter Weder, Wolfgang Jungraithmayr
OBJECTIVES: We showed previously that stromal cell-derived factor 1 (SDF-1) is a substrate of cluster of differentiation 26/dipeptidylpeptidase 4 (CD26/DPP4) and exerts regenerative properties on acute lung ischemia-reperfusion injury on CD26/DPP4 inhibition. Here, we extend our studies to test whether an intermediate recovery of lung transplants from ischemia/reperfusion injury by CD26/DPP4 inhibition can be achieved for up to 14 days. METHODS: Syngeneic mouse lung transplantation (Tx) was performed in C57BL/6 and in CD26-/- mice by applying 18 hours of cold ischemia...
November 15, 2016: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27933776/regulation-of-a-coupled-marcks-pi3k-lipid-kinase-circuit-by-calmodulin-single-molecule-analysis-of-a-membrane-bound-signaling-module
#7
Brian P Ziemba, G Hayden Swisher, Glenn Masson, John E Burke, Roger L Williams, Joseph J Falke
Amoeboid cells that employ chemotaxis to travel up an attractant gradient possess a signaling network assembled on the leading edge of the plasma membrane that senses the gradient and remodels the actin mesh and cell membrane to drive movement in the appropriate direction. In leukocytes such as macrophages and neutrophils, and perhaps in other amoeboid cells as well, the leading edge network includes a positive feedback loop in which the signaling of multiple pathway components is cooperatively coupled. Cytoplasmic Ca(2+) is a recently recognized component of the feedback loop at the leading edge where it stimulates phosphoinositide-3-kinase (PI3K) and the production of its product signaling lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3)...
November 22, 2016: Biochemistry
https://www.readbyqxmd.com/read/27932459/basophil-specific-protease-mmcp-8-provokes-an-inflammatory-response-in-the-skin-with-microvascular-hyperpermeability-and-leukocyte-infiltration
#8
Hidemitsu Tsutsui, Yoshinori Yamanishi, Hiromi Ohtsuka, Shingo Sato, Soichiro Yoshikawa, Hajime Karasuyama
Basophils have often been considered erroneously as minor relatives or blood-circulating precursors of tissue-resident mast cells, because of some phenotypic similarity between them, including basophilic secretory granules in the cytoplasm. However, recent studies revealed that the repertoire of serine proteases stored in secretory granules is distinct between them. Particularly, mouse mast cell protease 8 (mMCP-8) is specifically expressed by basophils but not mast cells in spite of its name. Therefore, mMCP-8 is commonly used as a basophil-specific marker while its functional property remains uncertain...
December 8, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913633/chemorepellent-semaphorin-3e-negatively-regulates-neutrophil-migration-in-vitro-and-in-vivo
#9
Hesam Movassagh, Abeer Saati, Saravanan Nandagopal, Ashfaque Mohammed, Nazanin Tatari, Lianyu Shan, Jonathan S Duke-Cohan, Keith R Fowke, Francis Lin, Abdelilah S Gounni
Neutrophil migration is an essential step in leukocyte trafficking during inflammatory responses. Semaphorins, originally discovered as axon guidance cues in neural development, have been shown to regulate cell migration beyond the nervous system. However, the potential contribution of semaphorins in the regulation of neutrophil migration is not well understood. This study examines the possible role of a secreted chemorepellent, Semaphorin 3E (Sema3E), in neutrophil migration. In this study, we demonstrated that human neutrophils constitutively express Sema3E high-affinity receptor, PlexinD1...
December 2, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27911604/neutrophil-elastase-activity-is-associated-with-exacerbations-and-lung-function-decline-in-bronchiectasis
#10
James D Chalmers, Kelly L Moffitt, Guillermo Suarez-Cuartin, Oriol Sibila, Simon Finch, Elizabeth Furrie, Alison Dicker, Karolina Wrobel, J Stuart Elborn, Brian Walker, S Lorraine Martin, Sara E Marshall, Jeffrey T-J Huang, Thomas C Fardon
RATIONALE: Sputum neutrophil elastase and serum desmosine, a linked marker of endogenous elastin degradation, are possible biomarkers of disease severity and progression in bronchiectasis. This study aimed to determine the association of elastase activity and desmosine with exacerbations and lung function decline in bronchiectasis. METHODS: This was a single-centre prospective cohort study using the TAYBRIDGE registry in Dundee, UK. 433 patients with HRCT-confirmed bronchiectasis provided blood samples for desmosine measurement and 381 provided sputum for baseline elastase activity measurements using an activity based immunosassay and fluorometric substrate assay...
December 2, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27845343/directed-transport-of-neutrophil-derived-extracellular-vesicles-enables-platelet-mediated-innate-immune-response
#11
Jan Rossaint, Katharina Kühne, Jennifer Skupski, Hugo Van Aken, Mark R Looney, Andres Hidalgo, Alexander Zarbock
The innate immune response to bacterial infections requires the interaction of neutrophils and platelets. Here, we show that a multistep reciprocal crosstalk exists between these two cell types, ultimately facilitating neutrophil influx into the lung to eliminate infections. Activated platelets adhere to intravascular neutrophils through P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1)-mediated binding, a primary interaction that allows platelets glycoprotein Ibα (GPIbα)-induced generation of neutrophil-derived extracellular vesicles (EV)...
November 15, 2016: Nature Communications
https://www.readbyqxmd.com/read/27826293/assessing-marine-microbial-induced-corrosion-at-santa-catalina-island-california
#12
Gustavo A Ramírez, Colleen L Hoffman, Michael D Lee, Ryan A Lesniewski, Roman A Barco, Arkadiy Garber, Brandy M Toner, Charles G Wheat, Katrina J Edwards, Beth N Orcutt
High iron and eutrophic conditions are reported as environmental factors leading to accelerated low-water corrosion, an enhanced form of near-shore microbial induced corrosion. To explore this hypothesis, we deployed flow-through colonization systems in laboratory-based aquarium tanks under a continuous flow of surface seawater from Santa Catalina Island, CA, USA, for periods of 2 and 6 months. Substrates consisted of mild steel - a major constituent of maritime infrastructure - and the naturally occurring iron sulfide mineral pyrite...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27818081/enhanced-sensitivity-of-neil1-mice-to-chronic-uvb-exposure
#13
Marcus J Calkins, Vladimir Vartanian, Nichole Owen, Guldal Kirkali, Pawel Jaruga, Miral Dizdaroglu, Amanda K McCullough, R Stephen Lloyd
Oxidative stress and reactive oxygen species (ROS)-induced DNA base damage are thought to be central mediators of UV-induced carcinogenesis and skin aging. However, increased steady-state levels of ROS-induced DNA base damage have not been reported after chronic UV exposure. Accumulation of ROS-induced DNA base damage is governed by rates of lesion formation and repair. Repair is generally performed by Base Excision Repair (BER), which is initiated by DNA glycosylases, such as 8-oxoguanine glycosylase and Nei-Endonuclease VIII-Like 1 (NEIL1)...
October 28, 2016: DNA Repair
https://www.readbyqxmd.com/read/27792201/preparation-characterization-and-activity-of-a-peptide-cellulosic-aerogel-protease-sensor-from-cotton
#14
J Vincent Edwards, Krystal R Fontenot, Nicolette T Prevost, Nicole Pircher, Falk Liebner, Brian D Condon
Nanocellulosic aerogels (NA) provide a lightweight biocompatible material with structural properties, like interconnected high porosity and specific surface area, suitable for biosensor design. We report here the preparation, characterization and activity of peptide-nanocellulose aerogels (PepNA) made from unprocessed cotton and designed with protease detection activity. Low-density cellulosic aerogels were prepared from greige cotton by employing calcium thiocyanate octahydrate/lithium chloride as a direct cellulose dissolving medium...
October 26, 2016: Sensors
https://www.readbyqxmd.com/read/27746119/development-of-the-first-internally-quenched-fluorescent-substrates-of-human-cathepsin-c-the-application-in-the-enzyme-detection-in-biological-samples
#15
Monika Łęgowska, Yveline Hamon, Anna Wojtysiak, Renata Grzywa, Marcin Sieńczyk, Timo Burster, Brice Korkmaz, Adam Lesner
Cathepsin C is a widely expressed cysteine exopeptidase that is mostly recognized for the activation of the granule-associated proinflammatory serine proteases in neutrophils, cytotoxic T lymphocytes and mast cells. It has been shown that the enzyme can be secreted extracellularly; however, its occurrence in human bodily fluids/physiological samples has not been thoroughly studied. In the course of this study, the first fluorescence resonance energy transfer peptides for the measurement of the activity of human cathepsin C were designed and synthesized...
October 13, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27726789/the-nadph-oxidase-and-microbial-killing-by-neutrophils-with-a-particular-emphasis-on-the-proposed-antimicrobial-role-of-myeloperoxidase-within-the-phagocytic-vacuole
#16
Adam P Levine, Anthony W Segal
This review is devoted to a consideration of the way in which the NADPH oxidase of neutrophils, NOX2, functions to enable the efficient killing of bacteria and fungi. It includes a critical examination of the current dogma that its primary purpose is the generation of hydrogen peroxide as substrate for myeloperoxidase-catalyzed generation of hypochlorite. Instead, it is demonstrated that NADPH oxidase functions to optimize the ionic and pH conditions within the vacuole for the solubilization and optimal activity of the proteins released into this compartment from the cytoplasmic granules, which kill and digest the microbes...
August 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/27698010/circulating-soluble-il-6r-but-not-adam17-activation-drives-mononuclear-cell-migration-in-tissue-inflammation
#17
Neele Schumacher, Stefanie Schmidt, Jeanette Schwarz, Dana Dohr, Juliane Lokau, Jürgen Scheller, Christoph Garbers, Athena Chalaris, Stefan Rose-John, Björn Rabe
Neutrophil and mononuclear cell infiltration during inflammatory processes is highly regulated. The first cells at the site of infection or inflammation are neutrophils, followed by mononuclear cells. IL-6 plays an important role during inflammatory states. It has been shown in several models that the soluble form of IL-6R (sIL-6R) is involved in the recruitment of mononuclear cells by a mechanism called IL-6 trans-signaling. It had been speculated that sIL-6R was generated at the site of inflammation by shedding from neutrophils via activation of the metalloprotease ADAM17...
October 3, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27693468/parkin-regulates-lipopolysaccharide-induced-proinflammatory-responses-in-acute-lung-injury
#18
Eleftheria Letsiou, Saad Sammani, Huashan Wang, Patrick Belvitch, Steven M Dudek
The acute respiratory distress syndrome (ARDS) is a serious condition resulting from direct or indirect lung injury that is associated with high mortality and morbidity. A key biological event in the pathogenesis of the acute lung injury (ALI) that causes acute respiratory distress syndrome is activation of the lung endothelium cells (ECs), which is triggered by a variety of inflammatory insults leading to barrier disruption and excessive accumulation of neutrophils. Recently, we demonstrated that imatinib protects against lipopolysaccharide (LPS)-induced EC activation by inhibiting c-Abl kinase...
September 13, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27676391/the-role-of-neutrophil-proteins-on-the-amyloid-beta-rage-axis
#19
Amanda J Stock, Anne Kasus-Jacobi, Jonathan D Wren, Virginie H Sjoelund, Glenn D Prestwich, H Anne Pereira
We previously showed an elevated expression of the neutrophil protein, cationic antimicrobial protein of 37kDa (CAP37), in brains of patients with Alzheimer's disease (AD), suggesting that CAP37 could be involved in AD pathogenesis. The first step in determining how CAP37 might contribute to AD pathogenesis was to identify the receptor through which it induces cell responses. To identify a putative receptor, we performed GAMMA analysis to determine genes that positively correlated with CAP37 in terms of expression...
2016: PloS One
https://www.readbyqxmd.com/read/27648695/tranexamic-acid-attenuates-the-loss-of-lung-barrier-function-in-a-rat-model-of-polytrauma-and-hemorrhage-with-resuscitation
#20
Xiaowu Wu, Michael A Dubick, Martin G Schwacha, Andrew P Cap, Daniel N Darlington
INTRODUCTION: Severe trauma, hemorrhage and resuscitation can lead to a trauma related acute lung injury that involves rapid infiltration of immune cells and platelets. This infiltration involves exymatic degradation of matrix proteins, including plasmin, and causes loss of barrier function. Since tranexamic acid (TXA) inhibits plasminogen/ plasmin binding to target substrates, it may attenuate loss of barrier function after severe trauma, hemorrhage and resuscitation. METHODS: Sprague-Dawley rats were subjected to polytrauma (laparotomy, and trauma to intestines, liver, right leg skeletal muscle and right femur fracture), then bled 40% of their blood volume...
September 19, 2016: Shock
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