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https://www.readbyqxmd.com/read/28619950/how-neutrophils-resist-shear-stress-at-blood-vessel-walls-molecular-mechanisms-subcellular-structures-and-cell-cell-interactions
#1
REVIEW
Daniela Begandt, Sarah Thome, Markus Sperandio, Barbara Walzog
Neutrophils are the first cells arriving at sites of tissue injury or infection to combat invading pathogens. Successful neutrophil recruitment to sites of inflammation highly depends on specific molecular mechanisms, fine-tuning the received information into signaling pathways and converting them into well-described recruitment steps. This review highlights the impact of vascular flow conditions on neutrophil recruitment and the multitude of mechanisms developed to enable this sophisticated process under wall shear stress conditions...
June 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28600292/adam10-interacting-tetraspanins-tspan5-and-tspan17-regulate-ve-cadherin-expression-and-promote-t-lymphocyte-transmigration
#2
Jasmeet S Reyat, Myriam Chimen, Peter J Noy, Justyna Szyroka, G Ed Rainger, Michael G Tomlinson
The recruitment of blood leukocytes across the endothelium to sites of tissue infection is central to inflammation, but also promotes chronic inflammatory diseases. A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane molecular scissor that is implicated in leukocyte transmigration by proteolytically cleaving its endothelial substrates. These include VE-cadherin, a homotypic adhesion molecule that regulates endothelial barrier function, and transmembrane chemokines CX3CL1 and CXCL16, which have receptors on leukocytes...
June 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28587841/3-nucleotidase-nuclease-in-protozoan-parasites-molecular-and-biochemical-properties-and-physiological-roles
#3
Anita Leocadio Freitas-Mesquita, José Roberto Meyer-Fernandes
3'-nucleotidase/nuclease (3'NT/NU) is a bi-functional enzyme that is able to hydrolyze 3'-monophosphorylated nucleotides and nucleic acids. This review summarizes the major molecular and biochemical properties of this enzyme in different trypanosomatid species. Sequence analysis of the gene encoding 3'NT/NU in Leishmania and Crithidia species showed that the protein possesses five highly conserved regions that are characteristic of members of the class I nuclease family. 3'NT/NU presents a molecular weight of approximately 40 kDa, which is conserved among the studied species...
June 3, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28553292/asct2-slc1a5-deficient-mice-have-normal-b-cell-development-proliferation-and-antibody-production
#4
Etienne Masle-Farquhar, Angelika Bröer, Mehmet Yabas, Anselm Enders, Stefan Bröer
SLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5's primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28552694/mesna-2-mercaptoethane-sodium-sulfonate-functions-as-a-regulator-of-myeloperoxidase
#5
Roohi Jeelani, Seyedehameneh Jahanbakhsh, Hamid-Reza Kohan-Ghadr, Mili Thakur, Sana Khan, Sarah R Aldhaheri, Zhe Yang, Peter Andreana, Robert Morris, Husam M Abu-Soud
Myeloperoxidase (MPO), an abundant protein in neutrophils, monocytes, and macrophages, is thought to play a critical role in the pathogenesis of various disorders ranging from cardiovascular diseases to cancer. We show that mesna (2-mercaptoethanesulfonic acid sodium salt), a detoxifying agent, which inhibits side effects of oxazaphosphorine chemotherapy, functions as a potent inhibitor of MPO; modulating its catalytic activity and function. Using rapid kinetic methods, we examined the interactions of mesna with MPO compounds I and II and ferric forms in the presence and absence of chloride (Cl(-)), the preferred substrate of MPO...
May 25, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28550118/s100a9-potentiates-the-activation-of-neutrophils-by-the-etiological-agent-of-gout-monosodium-urate-crystals
#6
Louis-Simon Rousseau, Guillaume Paré, Asmaa Lachhab, Paul H Naccache, François Marceau, Philippe Tessier, Martin Pelletier, Maria Fernandes
Gout is one of the most painful types of arthritis that arises when the body mounts an acute inflammatory reaction against a crystallized form of uric acid known as monosodium urate crystals (MSUs). Although MSUs are known to activate neutrophils, the most abundant leukocyte in the synovial fluid of patients with gout, few studies have investigated the effect on neutrophils of the simultaneous stimulation with MSU and proinflammatory mediators in the inflamed joint. Herein, we focused on a protein that is highly expressed in the synovium in gout, S100A9...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28524191/thermal-scribing-to-prototype-plastic-microfluidic-devices-applied-to-study-the-formation-of-neutrophil-extracellular-traps
#7
Arvind Chandrasekaran, Nikita Kalashnikov, Roni Rayes, Claire Wang, Jonathan Spicer, Christopher Moraes
Innovation in microfluidics-based biological research has been aided by the growing accessibility of versatile microscale fabrication techniques, particularly in rapid prototyping of elastomeric polydimethylsiloxane (PDMS) based devices. However, the use of PDMS presents considerable and often unexpected limitations, particularly in interpreting and validating biological data. To rapidly prototype microfluidic culture systems in conventional plastics commonly used in cell culture, we developed 'thermal scribing', a one-step micromachining technique in which thermoplastics are locally patterned by a heated tip, moving in user-controlled patterns...
May 31, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28522730/11%C3%AE-hsd1-suppresses-cardiac-fibroblast-cxcl2-cxcl5-and-neutrophil-recruitment-to-the-heart-post-mi
#8
Katie J Mylonas, Neil A Turner, Sumia A Bageghni, Christopher J Kenyon, Christopher I White, Kieran McGregor, Robert A Kimmitt, Richard Sulston, Valerie Kelly, Brian R Walker, Karen E Porter, Karen E Chapman, Gillian A Gray
We have previously demonstrated that neutrophil recruitment to the heart following myocardial infarction (MI) is enhanced in mice lacking 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that regenerates active glucocorticoid within cells from intrinsically inert metabolites. The present study aimed to identify the mechanism of regulation. In a mouse model of MI, neutrophil mobilization to blood and recruitment to the heart were higher in 11β-HSD1-deficient (Hsd11b1(-)(/)(-) ) relative to wild-type (WT) mice, despite similar initial injury and circulating glucocorticoid...
June 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28511370/correlation-of-plasma-neutrophil-elastase-activity-and-endogenous-protease-inhibitor-levels-with-the-severity-of-pre-eclampsia
#9
Mamatha Kunder, Av Moideen Kutty, V Lakshmaiah, S R Sheela
INTRODUCTION: Pre-eclampsia (PE) is a common maternal syndrome characterized by severe systemic inflammatory response including neutrophil activation leading to uncontrolled activity of elastase. The excessive activity of elastase would lead to destroyal of the integrity of endothelial cells and could exacerbate the pathophysiological symptoms in PE. Thus, assessment of NE activity and its control mechanisms would be of relevance in the determination of severity of PE. AIM: To correlate the activity of plasma NE and its endogenous inhibitors α1-antitrypsin (α1-AT) and α2-macroglobulin (α2-MG) with severity of PE...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28487846/ectodomain-shedding-by-adam17-its-role-in-neutrophil-recruitment-and-the-impairment-of-this-process-during-sepsis
#10
REVIEW
Hemant K Mishra, Jing Ma, Bruce Walcheck
Neutrophils are specialized at killing bacteria and are recruited from the blood in a rapid and robust manner during infection. A cascade of adhesion events direct their attachment to the vascular endothelium and migration into the underlying tissue. A disintegrin and metalloproteinase 17 (ADAM17) functions in the cell membrane of neutrophils and endothelial cells by cleaving its substrates, typically in a cis manner, at an extracellular site proximal to the cell membrane. This process is referred to as ectodomain shedding and it results in the downregulation of various adhesion molecules and receptors, and the release of immune regulating factors...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28464614/imaging-xps-and-photoemission-electron-microscopy-surface-chemical-mapping-and-blood-cell-visualization
#11
Andreas Skallberg, Caroline Brommesson, Kajsa Uvdal
Combined photoemission electron microscopy (PEEM) and imaging x-ray photoelectron spectroscopy (XPS), i.e., electron spectroscopy for chemical analysis in the nanoregion, has been used for surface characterization of bio-relevant and biological samples. In the first example, the authors prepared a gold patterned silicon substrate, stepwise surface modified by self-assembled monolayers followed by quantum dot (QDot) specific linking and investigated by means of work function mapping and elemental imaging in the submicrometer range...
May 2, 2017: Biointerphases
https://www.readbyqxmd.com/read/28462209/lung-ischemia-reperfusion-injury-the-therapeutic-role-of-dipeptidyl-peptidase-4-inhibition
#12
REVIEW
Paul A J Beckers, Jan F Gielis, Paul E Van Schil, Dirk Adriaensen
Dipeptidyl peptidase 4 (DPP4) is a cell surface protease that has been reported to play a role in glucose homeostasis, cancer, HIV, autoimmunity, immunology and inflammation. A role for DPP4 in ischemia-reperfusion injury (IRI) in the heart has been established. Dipeptidyl peptidase 4 inhibition (DPP4i) appeared to decrease infarct size, improves cardiac function and promotes myocardial regeneration. Lung ischemia reperfusion injury is caused by a complex mechanism in which macrophages and neutrophils play an important role...
March 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28450870/neutrophil-extracellular-traps-contain-selected-antigens-of-anti-neutrophil-cytoplasmic-antibodies
#13
Rachita Panda, Thorsten Krieger, Luke Hopf, Thomas Renné, Friedrich Haag, Nadja Röber, Karsten Conrad, Elena Csernok, Tobias A Fuchs
Neutrophil extracellular traps (NETs) are chromatin filaments decorated with enzymes from neutrophil cytoplasmic granules. Anti-neutrophil cytoplasmic antibodies (ANCAs) bind to enzymes from neutrophil cytoplasmic granules and are biomarkers for the diagnosis of systemic vasculitides. ANCA diagnostics are based on indirect immunofluorescence (IIF) of ethanol-fixed neutrophils. IIF shows a cytoplasmic staining pattern (C-ANCA) due to autoantibodies against proteinase 3 (PR3) or a perinuclear staining pattern (P-ANCA) due to autoantibodies against myeloperoxidase (MPO)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28428204/flow-perturbation-mediates-neutrophil-recruitment-and-potentiates-endothelial-injury-via-tlr2-in-mice-implications-for-superficial-erosion
#14
Grégory Franck, Thomas Mawson, Grasiele Sausen, Manuel Salinas, Gustavo Santos Masson, Andrew P Cole, Marina Beltrami Moreira, Yiannis Chatzizisis, Thibaut Quillard, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K Sukhova, Filip K Swirski, Matthias Nahrendorf, Elena Aikawa, Kevin Croce, Peter Libby
Rationale: Superficial erosion currently causes up to a third of acute coronary syndromes (ACS), yet we lack understanding of its mechanisms. Thrombi due to superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. Objective: This study tested in vivo the involvement of disturbed flow, and of neutrophils, hyaluronan, and TLR2 ligation in superficial intimal injury, a process implicated in superficial erosion. Methods and Results: In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell (EC) activation, neutrophil accumulation, EC death and desquamation, and mural thrombosis...
April 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28418861/brain-derived-neurotrophic-factor-involved-epigenetic-repression-of-ugt2b7-in-colorectal-carcinoma-a-mechanism-to-alter-morphine-glucuronidation-in-tumor
#15
Zi-Zhao Yang, Li Li, Ming-Cheng Xu, Hai-Xing Ju, Miao Hao, Jing-Kai Gu, Zai-Jie Jim Wang, Hui-Di Jiang, Lu-Shan Yu, Su Zeng
Uridine diphosphate-glucuronosyltransferase (UGT) 2B7, as one of significant drug enzymes, is responsible on the glucuronidation of abundant endobiotics or xenobiotics. We here report that it is markedly repressed in the tumor tissues of colorectal carcinoma (CRC) patients. Accordingly, morphine in CRC cells will stimulate the expression of its main metabolic enzyme, UGT2B7 during tolerance generation by activating the positive signals in histone 3, especially for trimethylated lysine 27 (H3K4Me3) and acetylated lysine 4 (H3K27Ac)...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414448/substrate-profiling-and-high-resolution-co-complex-crystal-structure-of-a-secreted-c11-protease-conserved-across-commensal-bacteria
#16
Emily J Roncase, Clara Moon, Sandip Chatterjee, Gonzalo E González-Páez, Charles S Craik, Anthony J O'Donoghue, Dennis W Wolan
Cysteine proteases are among the most abundant hydrolytic enzymes produced by bacteria, and this diverse family of proteins have significant biological roles in bacterial viability and environmental interactions. Members of the clostripain-like (C11) family of cysteine proteases from commensal gut bacterial strains have recently been shown to mediate immune responses by inducing neutrophil phagocytosis and activating bacterial pathogenic toxins. Development of substrates, inhibitors, and probes that target C11 proteases from enteric bacteria will help to establish the role of these proteins at the interface of the host and microbiome in health and disease...
April 27, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28402950/lysosomal-lipid-hydrolysis-provides-substrates-for-lipid-mediator-synthesis-in-murine-macrophages
#17
Stefanie Schlager, Nemanja Vujic, Melanie Korbelius, Madalina Duta-Mare, Juliane Dorow, Christina Leopold, Silvia Rainer, Martin Wegscheider, Helga Reicher, Uta Ceglarek, Wolfgang Sattler, Branislav Radovic, Dagmar Kratky
Degradation of lysosomal lipids requires lysosomal acid lipase (LAL), the only intracellular lipase known to be active at acidic pH. We found LAL to be expressed in murine immune cells with highest mRNA expression in macrophages and neutrophils. Furthermore, we observed that loss of LAL in mice caused lipid accumulation in white blood cells in the peripheral circulation, which increased in response to an acute inflammatory stimulus. Lal-deficient (-/-) macrophages accumulate neutral lipids, mainly cholesteryl esters, within lysosomes...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28362108/alpha1-antitrypsin-deficient-macrophages-have-increased-matriptase-mediated-proteolytic-activity
#18
Karina Krotova, George W Marek, Rejean L Wang, George Aslanidi, Brad E Hoffman, Nazli Khodayari, Farshid N Rouhani, Mark L Brantly
Alpha1-antitrypsin (AAT) deficiency-associated emphysema is largely attributed to insufficient inhibition of neutrophil elastase released from neutrophils. Correcting AAT levels by augmentation therapy only slows disease progression; the absence of full recovery indicates a more complex process of lung destruction. Because alveolar macrophages (Mɸ) express AAT, we propose that the expression and intracellular accumulation of mutated Z-AAT (the most common mutation is called Z) compromise Mɸ function and contribute to emphysema development...
March 31, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28360423/immunometabolism-in-systemic-lupus-erythematosus
#19
REVIEW
Laurence Morel
Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by pathogenic autoantibodies directed against nucleoprotein complexes. Beyond the activation of autoreactive B cells, this process involves dysregulation in many other types of immune cells, including CD4(+) T cells, dendritic cells, macrophages and neutrophils. Metabolic substrate utilization and integration of cues from energy sensors are critical checkpoints of effector functions in the immune system, with common as well as cell-specific programmes...
March 31, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28230157/highly-sensitive-and-adaptable-fluorescence-quenched-pair-discloses-the-substrate-specificity-profiles-in-diverse-protease-families
#20
Marcin Poreba, Aleksandra Szalek, Wioletta Rut, Paulina Kasperkiewicz, Izabela Rutkowska-Wlodarczyk, Scott J Snipas, Yoshifumi Itoh, Dusan Turk, Boris Turk, Christopher M Overall, Leszek Kaczmarek, Guy S Salvesen, Marcin Drag
Internally quenched fluorescent (IQF) peptide substrates originating from FRET (Förster Resonance Energy Transfer) are powerful tool for examining the activity and specificity of proteases, and a variety of donor/acceptor pairs are extensively used to design individual substrates and combinatorial libraries. We developed a highly sensitive and adaptable donor/acceptor pair that can be used to investigate the substrate specificity of cysteine proteases, serine proteases and metalloproteinases. This novel pair comprises 7-amino-4-carbamoylmethylcoumarin (ACC) as the fluorophore and 2,4-dinitrophenyl-lysine (Lys(DNP)) as the quencher...
February 23, 2017: Scientific Reports
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