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https://www.readbyqxmd.com/read/28166238/integrin-dependent-cell-adhesion-to-neutrophil-extracellular-traps-through-engagement-of-fibronectin-in-neutrophil-like-cells
#1
Marcello Monti, Francesca Iommelli, Viviana De Rosa, Maria Vincenza Carriero, Roberta Miceli, Rosa Camerlingo, Giovanni Di Minno, Silvana Del Vecchio
Neutrophil extracellular traps (NETs), originally recognized as a host defense mechanism, were reported to promote thrombosis and metastatic dissemination of cancer cells. Here we tested the role of integrins α5β1 and ανβ3 in the adhesion of cancer cells to NETs. Neutrophil-like cells stimulated with calcium ionophore (A23187) were used as a stable source of cell-free NETs-enriched suspensions. Using NETs as an adhesion substrate, two human K562 cell lines, differentially expressing α5β1 and ανβ3 integrins, were subjected to adhesion assays in the presence or absence of DNAse 1, blocking antibodies against α5β1 or ανβ3, alone or in combination with DNAse 1, and Proteinase K...
2017: PloS One
https://www.readbyqxmd.com/read/28155729/mechanical-regulation-of-calcium-signaling-of-hl-60-on-p-selectin-under-flow
#2
Bing Huang, Yingchen Ling, Jiangguo Lin, Ying Fang, Jianhua Wu
BACKGROUND: Binding of P-selectin to P-selectin glycoprotein ligand-1 (PSGL-1) makes neutrophils roll on and adhere to inflammatory site. Intracellular calcium bursting of adhered neutrophils is a key event for subsequent arresting firmly at and migrating into the injured tissue. But, it remains unclear how the cytoplasmic calcium signaling of the cells were modulated by the fluid shear stress. Here, we focus on mechanical regulation of P-selectin-induced calcium signaling of neutrophil-like HL-60 cells under flow...
December 28, 2016: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28135312/inhibition-of-myeloperoxidase-activity-in-cystic-fibrosis-sputum-by-peptide-inhibitor-of-complement-c1-pic1
#3
Pamela S Hair, Laura A Sass, Neel K Krishna, Kenji M Cunnion
Myeloperoxidase is the major peroxidase enzyme in neutrophil granules and implicated in contributing to inflammatory lung damage in cystic fibrosis. Free myeloperoxidase is present in cystic fibrosis lung fluid and generates hypochlorous acid. Here we report a new inhibitor of myeloperoxidase activity, Peptide Inhibitor of Complement C1 (PIC1). Using TMB as the oxidizing substrate, PIC1 inhibited myeloperoxidase activity in cystic fibrosis sputum soluble fractions by an average of a 3.4-fold decrease (P = 0...
2017: PloS One
https://www.readbyqxmd.com/read/28132911/effect-of-alpha-lipoic-acid-on-leukotriene-a4-hydrolase
#4
María José Torres, Angélica Fierro, C David Pessoa-Mahana, Javier Romero-Parra, Gonzalo Cabrera, Mario Faúndez
Leukotriene A4 hydrolase is a soluble enzyme with epoxide hydrolase and aminopeptidase activities catalysing the conversion of leukotriene A4 to leukotriene B4 and the hydrolysis of the peptide proline-glycine-proline. Imbalances in leukotriene B4 synthesis are related to several pathologic conditions. Currently there are no available drugs capable to modulate the synthesis of leukotriene B4 or to block its receptors. Here we show the inhibitory profile of alpha lipoic acid on the activity of leukotriene A4 Hydrolase...
January 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28132723/eb1-contributes-to-proper-front-to-back-polarity-in-neutrophil-like-hl-60-cells
#5
Matthias Samereier, Michael Schleicher, Heike Roth, Doris Brechtefeld, Barbara Walzog, Annette Müller-Taubenberger
Directed migration of leukocytes towards a chemotactic source is largely dependent on coordinated actin cytoskeleton functions that provide the driving forces at the cell front and enable contractility at the rear. In contrast to the force-generating properties of the actin cytoskeleton, the microtubule network assumes a regulatory function in balancing front-to-back polarity. In migrating neutrophils, microtubules are mostly concentrated at the cell rear, and previously published work suggested that microtubules are stabilized and kept in place by a mechanism involving Cdc42, WASP, CD11b, and the end-binding protein 1 (EB1)...
January 19, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28122813/hs1-deficiency-impairs-neutrophil-recruitment-in-vivo-and-activation-of-the-small-gtpases-rac1-and-rap1
#6
Joanna Latasiewicz, Annette Artz, Ding Jing, Mariana Pacheco Blanco, Silke M Currie, Martha Velázquez Avila, Michael Schnoor, Dietmar Vestweber
Neutrophil extravasation is a critical step of the innate immune system's response to inflammation. This multistep process is tightly regulated by adhesion and signaling molecules in the endothelium and neutrophils. Activation of the β2 integrin LFA-1 is critical for adhesion of leukocytes to postcapillary venules. This step requires coordinated activation of signaling pathways in chemokine-stimulated neutrophils, including GTPase activation and cytoskeletal remodeling, leading to conformational changes in LFA-1...
January 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28119468/candida-albicans-chitin-increases-arginase-1-activity-in-human-macrophages-with-an-impact-on-macrophage-antimicrobial-functions
#7
Jeanette Wagener, Donna M MacCallum, Gordon D Brown, Neil A R Gow
: The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen...
January 24, 2017: MBio
https://www.readbyqxmd.com/read/28115520/cellular-uptake-and-delivery-of-myeloperoxidase-to-lysosomes-promotes-lipofuscin-degradation-and-lysosomal-stress-in-retinal-cells
#8
Gouri Yogalingam, Amanda R Lee, Donald S Mackenzie, Travis J Maures, Agnes Rafalko, Heather Prill, Geoffrey Berguig, Chuck Hague, Terri Christianson, Sean M Bell, Jonathon H LeBowitz
Neutrophil myeloperoxidase (MPO) catalyzes the H2O2-dependent oxidation of chloride anion to generate hypochlorous acid, a potent antimicrobial agent. Besides its well defined role in innate immunity, aberrant degranulation of neutrophils in several inflammatory diseases leads to redistribution of MPO to the extracellular space, where it can mediate tissue damage by promoting the oxidation of several additional substrates. Here, we demonstrate that mannose-6-phosphate (M6P) receptor-mediated cellular uptake and delivery of MPO to lysosomes of retinal pigmented epithelial (RPE) cells acts to clear this harmful enzyme from the extracellular space, with lysosomal-delivered MPO exhibiting a half-life of 10 hours...
January 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28115509/the-tat-substrate-sufi-is-critical-for-the-ability-of-yersinia-pseudotuberculosis-to-cause-systemic-infection
#9
Ummehan Avican, Tugrul Doruk, Yngve Östberg, Anna Fahlgren, Åke Forsberg
The Twin-arginine translocation (Tat) system targets folded proteins across the inner membrane and it is crucial for virulence in many important human pathogenic bacteria. Tat has been shown to be required for virulence of Yersinia pseudotuberculosis and we recently showed that the system is critical for different virulence related stress responses as well as for iron uptake. In this study, we wanted to address the role of the Tat substrates in in vivo virulence. Therefore, 22 genes encoding potential Tat substrates were mutated and each mutant was evaluated in competitive oral infection of mice...
January 23, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28096297/frontline-science-tumor-necrosis-factor-%C3%AE-stimulation-and-priming-of-human-neutrophil-granule-exocytosis
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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/the-basophil-specific-protease-mmcp-8-provokes-an-inflammatory-response-in-the-skin-with-microvascular-hyperpermeability-and-leukocyte-infiltration
#17
Hidemitsu Tsutsui, Yoshinori Yamanishi, Hiromi Ohtsuka, Shingo Sato, Soichiro Yoshikawa, Hajime Karasuyama
Basophils have often been erroneously considered to be 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 in them. Particularly, mouse mast cell protease 8 (mMCP-8) is specifically expressed by basophils but not mast cells despite its name. Therefore, mMCP-8 is commonly used as a basophil-specific marker, but its functional property remains uncertain...
January 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913633/chemorepellent-semaphorin-3e-negatively-regulates-neutrophil-migration-in-vitro-and-in-vivo
#18
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
#19
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
#20
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
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