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https://www.readbyqxmd.com/read/28615221/coronin-1a-a-novel-player-in-integrin-biology-controls-neutrophil-trafficking-in-innate-immunity
#1
Robert Pick, Daniela Begandt, Thomas J Stocker, Melanie Salvermoser, Sarah Thome, Ralph T Böttcher, Eloi Montanez, Ute Harrison, Ignasi Forné, Alexander G Khandoga, Raffaele Coletti, Ludwig T Weckbach, Doris Brechtefeld, Rainer Haas, Axel Imhof, Steffen Massberg, Markus Sperandio, Barbara Walzog
Trafficking of polymorphonuclear neutrophils (PMNs) during inflammation critically depends on the β2 integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18). Here, we identify Coronin 1A (Coro1A) as a novel regulator of β2 integrins that interacts with the cytoplasmic tail of CD18 and is crucial for induction of PMN adhesion and post-adhesion events, including adhesion strengthening, spreading, and migration under flow conditions. Transition of PMN rolling to firm adhesion critically depends on Coro1A by regulating the accumulation of high affinity LFA-1 in focal zones of adherent cells...
June 14, 2017: Blood
https://www.readbyqxmd.com/read/28555620/leukocyte-integrin-mac-1-regulates-thrombosis-via-interaction-with-platelet-gpib%C3%AE
#2
Yunmei Wang, Huiyun Gao, Can Shi, Paul W Erhardt, Alexander Pavlovsky, Dmitry A Soloviev, Kamila Bledzka, Valentin Ustinov, Liang Zhu, Jun Qin, Adam D Munday, Jose Lopez, Edward Plow, Daniel I Simon
Inflammation and thrombosis occur together in many diseases. The leukocyte integrin Mac-1 (also known as integrin αMβ2, or CD11b/CD18) is crucial for leukocyte recruitment to the endothelium, and Mac-1 engagement of platelet GPIbα is required for injury responses in diverse disease models. However, the role of Mac-1 in thrombosis is undefined. Here we report that mice with Mac-1 deficiency (Mac-1(-/-)) or mutation of the Mac-1-binding site for GPIbα have delayed thrombosis after carotid artery and cremaster microvascular injury without affecting parameters of haemostasis...
May 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28450419/phosphoproteome-analysis-reveals-differential-mode-of-action-of-sorafenib-in-wildtype-and-mutated-flt3-aml-cells
#3
Catrin Roolf, Nikolaj Dybowski, Anett Sekora, Stefan Mueller, Gudrun Knuebel, Andreas Tebbe, Hugo Murua Escobar, Klaus Godl, Christian Junghanss, Christoph Schaab
Constitutively activating internal tandem duplication (ITD) alterations of the receptor tyrosine kinase FLT3 (Fms-like tyrosine kinase 3) are common in acute myeloid leukemia (AML) and classifies FLT3 as an attractive therapeutic target. So far, applications of FLT3 small molecule inhibitors have been investigated primarily in FLT3-ITD+ patients. Only recently, a prolonged event-free survival has been observed in AML patients who were treated with the multi-kinase inhibitor sorafenib in addition to standard therapy...
April 27, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28434729/effects-of-intrauterine-infusion-of-escherichia-coli-lipopolysaccharide-on-uterine-mrna-gene-expression-and-peripheral-polymorphonuclear-leukocytes-in-jersey-cows-diagnosed-with-purulent-vaginal-discharge
#4
João G N Moraes, Luís G D Mendonça, Paula R B Silva, Alexandre A Scanavez, Klibs N Galvão, Michael A Ballou, Milli Worku, Ricardo C Chebel
The objectives of the current experiment were to investigate the effects of intrauterine treatment of cows with purulent vaginal discharge (PVD) using lipopolysaccharide (LPS) from Escherichia coli on uterine mRNA expression of genes related to inflammatory responses, peripheral polymorphonuclear leukocyte (PMN) function, hematological parameters, and blood concentrations of cortisol, haptoglobin, and progesterone (P4). Jersey cows (n = 3,084) were examined for PVD at 35 ± 6 d postpartum using the Metricheck device (Simcro, Hamilton, New Zealand)...
April 20, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28424516/slamf7-is-critical-for-phagocytosis-of-haematopoietic-tumour-cells-via-mac-1-integrin
#5
Jun Chen, Ming-Chao Zhong, Huaijian Guo, Dominique Davidson, Sabrin Mishel, Yan Lu, Inmoo Rhee, Luis-Alberto Pérez-Quintero, Shaohua Zhang, Mario-Ernesto Cruz-Munoz, Ning Wu, Donald C Vinh, Meenal Sinha, Virginie Calderon, Clifford A Lowell, Jayne S Danska, André Veillette
Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo, suggesting that blockade of the SIRPα-CD47 checkpoint could be useful in treating human cancer...
April 27, 2017: Nature
https://www.readbyqxmd.com/read/28408624/activated-protein-c-inhibits-neutrophil-extracellular-trap-formation-in-vitro-and-activation-in-vivo
#6
Laura D Healy, Cristina Puy, José A Fernández, Annachiara Mitrugno, Ravi S Keshari, Nyiawung A Taku, Tiffany T Chu, Xiao Xu, András Gruber, Florea Lupu, John H Griffin, Owen J T McCarty
Activated protein C (APC) is a multifunctional serine protease with anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to the cytoprotective effects of APC on endothelial cells, podocytes, and neurons, APC cleaves and detoxifies extracellular histones, a major component of neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also can lead to thrombosis; the pathways that negatively regulate NETosis are largely unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis via receptor-mediated cell signaling mechanisms...
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28396322/cyclic-amp-elevating-capacity-of-adenylate-cyclase-toxin-hemolysin-is-sufficient-for-lung-infection-but-not-for-full-virulence-of-bordetella-pertussis
#7
Karolina Skopova, Barbora Tomalova, Ivan Kanchev, Pavel Rossmann, Martina Svedova, Irena Adkins, Ilona Bibova, Jakub Tomala, Jiri Masin, Nicole Guiso, Radim Osicka, Radislav Sedlacek, Marek Kovar, Peter Sebo
The adenylate cyclase toxin-hemolysin (CyaA, ACT, or AC-Hly) of Bordetella pertussis targets phagocytic cells expressing the complement receptor 3 (CR3, Mac-1, αMβ2 integrin, or CD11b/CD18). CyaA delivers into cells an N-terminal adenylyl cyclase (AC) enzyme domain that is activated by cytosolic calmodulin and catalyzes unregulated conversion of cellular ATP into cyclic AMP (cAMP), a key second messenger subverting bactericidal activities of phagocytes. In parallel, the hemolysin (Hly) moiety of CyaA forms cation-selective hemolytic pores that permeabilize target cell membranes...
June 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28370678/wound-healing-in-mac-1-deficient-mice
#8
Lin Chen, Sridevi Nagaraja, Jian Zhou, Yan Zhao, David Fine, Alexander Y Mitrophanov, Jaques Reifman, Luisa A DiPietro
Mac-1 (CD11b/CD18) is a macrophage receptor that plays several critical roles in macrophage recruitment and activation. Because macrophages are essential for proper wound healing, the impact of Mac-1 deficiency on wound healing is of significant interest. Prior studies have shown that Mac-1(-/-) mice exhibit deficits in healing, including delayed wound closure in scalp and ear wounds. This study examined whether Mac-1 deficiency influences wound healing in small excisional and incisional skin wounds. Three millimeter diameter full thickness excisional wounds and incisional wounds were prepared on the dorsal skin of Mac-1 deficient (Mac-1(-/-) ) and wild type (WT) mice, and wound healing outcomes were examined...
April 1, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28362031/comparison-of-anaesthetic-gas-consumption-and-stability-of-anaesthesia-using-automatic-and-manual-control-over-the-course-of-anaesthesia
#9
Tomasz Skalec, Agnieszka Górecka-Dolny, Stanisław Zieliński, Mirosław Gibek, Łukasz Stróżecki, Andrzej Kübler
BACKGROUND: The automatic control module of end-tidal volatile agents (EtC) was designed to reduce the consumption of anaesthetic gases, increase the stability of general anaesthesia and reduce the need for adjustments in the settings of the anaesthesia machine. The aim of this study was to verify these hypotheses. METHODS: The course of general anaesthesia with the use of the EtC module was analysed for haemodynamic stability, depth of anaesthesia, end-expiratory concentration of anaesthetic, number of ventilator key presses, fentanyl supply, consumption of volatile agents and anaesthesia and operation times...
2017: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/28351497/a-preferential-delivery-method-to-investigate-direct-neuromuscular-blockade-effect-of-inhaled-anesthetics-on-skeletal-muscle
#10
Ling Ye, Pingliang Yang
Inhaled anesthetics can enhance the effect of neuromuscular blocker, but whether inhaled anesthetics such as sevoflurane have a direct effect on skeletal muscle contractility is unknown. Selectively blocking skeletal muscle may prevent the interference effect of central nervous system. So we decided to evaluate a local application of neuromuscular blocker (NMB) atracurium to prevent the general effect on skeletal muscle. In part 1, sevoflurane (a inhaled anesthetic) minimum alveolar concentrations (MAC) of 1...
April 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28343767/neural-cell-adhesion-molecule-expression-in-dilated-cardiomyopathy-is-associated-with-intramyocardial-inflammation-and-hypertrophy
#11
Karsten Ostermann, Heinz-Peter Schultheiss, Michel Noutsias
Chronic intramyocardial inflammation (inflammatory cardiomyopathy/DCMi) is linked to the pathogenesis of dilated cardiomyopathy (DCM). Neural cell adhesion molecule (NCAM) is involved in orchestrating cardiac muscle morphogenesis, but is down-regulated after embryogenesis. We investigated NCAM expression in adult DCM hearts, its possible association with DCMi-parameters, and with cardiomyocyte hypertrophy (CMH). Endomyocardial biopsies (EMBs) from DCM patients (n=85; n=37 females; age: 48±19years; LVEF <40%) and controls from non-cardiac deaths were immunostained for DCMi markers and for NCAM expression, and quantified by digital image analysis (DIA)...
March 18, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28340410/development-of-fusogenic-glass-surfaces-that-impart-spatiotemporal-control-over-macrophage-fusion-direct-visualization-of-multinucleated-giant-cell-formation
#12
James J Faust, Wayne Christenson, Kyle Doudrick, Robert Ros, Tatiana P Ugarova
Implantation of synthetic material, including vascular grafts, pacemakers, etc. results in the foreign body reaction and the formation of multinucleated giant cells (MGCs) at the exterior surface of the implant. Despite the long-standing premise that fusion of mononucleated macrophages results in the formation of MGCs, to date, no published study has shown fusion in context with living specimens. This is due to the fact that optical-quality glass, which is required for the majority of live imaging techniques, does not promote macrophage fusion...
June 2017: Biomaterials
https://www.readbyqxmd.com/read/28292981/vaginal-heparan-sulfate-linked-to-neutrophil-dysfunction-in-the-acute-inflammatory-response-associated-with-experimental-vulvovaginal-candidiasis
#13
Junko Yano, Mairi C Noverr, Paul L Fidel
Despite acute inflammation by polymorphonuclear neutrophils (PMNs) during vulvovaginal candidiasis (VVC), clearance of Candida fails to occur. The purpose of this study was to uncover the mechanism of vaginal PMN dysfunction. Designs included assessing PMN migration, proinflammatory mediators, and tissue damage (by analysis of the activity of lactate dehydrogenase [LDH]) in mice susceptible (C3H/HeN-C57BL/6) or resistant (CD-1) to chronic VVC (CVVC-S or CVVC-R) and testing morphology-specific Candida albicans strains under conditions of preinduced PMN migration (CVVC-S mice) or PMN depletion (CVVC-R mice)...
March 14, 2017: MBio
https://www.readbyqxmd.com/read/28287124/endogenous-tnf%C3%AE-orchestrates-the-trafficking-of-neutrophils-into-and-within-lymphatic-vessels-during-acute-inflammation
#14
Samantha Arokiasamy, Christian Zakian, Jessica Dilliway, Wen Wang, Sussan Nourshargh, Mathieu-Benoit Voisin
Neutrophils are recognised to play a pivotal role at the interface between innate and acquired immunities following their recruitment to inflamed tissues and lymphoid organs. While neutrophil trafficking through blood vessels has been extensively studied, the molecular mechanisms regulating their migration into the lymphatic system are still poorly understood. Here, we have analysed neutrophil-lymphatic vessel interactions in real time and in vivo using intravital confocal microscopy applied to inflamed cremaster muscles...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28283350/ultrafine-carbon-particles-promote-rotenone-induced-dopamine-neuronal-loss-through-activating-microglial-nadph-oxidase
#15
Yinxi Wang, Dan Liu, Huifeng Zhang, Yixin Wang, Ling Wei, Yutong Liu, Jieying Liao, Hui-Ming Gao, Hui Zhou
BACKGROUND: Atmospheric ultrafine particles (UFPs) and pesticide rotenone were considered as potential environmental risk factors for Parkinson's disease (PD). However, whether and how UFPs alone and in combination with rotenone affect the pathogenesis of PD remains largely unknown. METHODS: Ultrafine carbon black (ufCB, a surrogate of UFPs) and rotenone were used individually or in combination to determine their roles in chronic dopaminergic (DA) loss in neuron-glia, and neuron-enriched, mix-glia cultures...
May 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28245370/-establishment-and-identification-of-scl-tta-bcr-abl-transgenic-mouse-model-with-chronic-myeloid-leukemia
#16
Yan Lin, Wei Fu, Ying-Min Liang
OBJECTIVE: To establish transgenic mouse model with chronic myeloid leukemia(CML) by tetracycline withdrawal, so as to provide the experimental tool for studying pathogenesis of CML and searching new therapeutic method for this disease. METHODS: The BCR-ABL expression in stem and progenitor cells in SCL-tTA/BCR-ABL transgenic mice was induced by tetracycline withdrawal in drinking water; and the peripheral hemogram and spleen index were examined after identifying genotypes in mice; the distribution of hematopoietic lineage in bone marrow, spleen and peripheral blood was detected by flow cytometry...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28219886/dependence-of-glomerulonephritis-induction-on-novel-intraglomerular-alternatively-activated-bone-marrow-derived-macrophages-and-mac-1-and-pd-l1-in-lupus-prone-nzm2328-mice
#17
Sun-Sang J Sung, Yan Ge, Chao Dai, Hongyang Wang, Shu Man Fu, Rahul Sharma, Young S Hahn, Jing Yu, Thu H Le, Mark D Okusa, Warren K Bolton, Jessica R Lawler
Glomerular damage mediated by glomerulus-infiltrating myeloid-derived cells is a key pathogenic event in lupus nephritis (LN), but the process is poorly understood. Confocal microscopy of kidney sections and flow cytometry analysis of glomerular cells from magnetic bead-purified glomeruli have identified glomerulus-infiltrating leukocyte populations in NZM2328 (NZM) lupus-prone mice with spontaneous chronic glomerulonephritis (GN) and anti-glomerular basement membrane-induced nephritis. The occurrence of a major glomerulus-infiltrating CD11b(+)F4/80(-)I-A(-) macrophage population exhibiting the markers programmed death ligand-1 (PD-L1), Mac-2, and macrophage mannose receptor (CD206) and producing Klf4, Il10, Retnla, Tnf, and Il6 mRNA, which are known to be expressed by alternatively activated (M2b) macrophages, correlated with proteinuria status...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28160743/dioxolanea3-phosphatidylethanolamines-are-generated-by-human-platelets-and-stimulate-neutrophil-integrin-expression
#18
Maceler Aldrovandi, Christine Hinz, Sarah N Lauder, Helen Podmore, Martin Hornshaw, David A Slatter, Victoria J Tyrrell, Stephen R Clark, Lawrence J Marnett, Peter W Collins, Robert C Murphy, Valerie B O'Donnell
Activated platelets generate an eicosanoid proposed to be 8-hydroxy-9,10-dioxolane A3 (DXA3). Herein, we demonstrate that significant amounts of DXA3 are rapidly attached to phosphatidylethanolamine (PE) forming four esterified eicosanoids, 16:0p, 18:0p, 18:1p and 18:0a/DXA3-PEs that can activate neutrophil integrin expression. These lipids comprise the majority of DXA3 generated by platelets, are formed in ng amounts (24.3±6.1ng/2×10(8)) and remain membrane bound. Pharmacological studies revealed DXA3-PE formation involves cyclooxygenase-1 (COX), protease-activated receptors (PAR) 1 and 4, cytosolic phospholipase A2 (cPLA2), phospholipase C and intracellular calcium...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28090458/efficient-isolation-of-sperm-with-high-dna-integrity-and-stable-chromatin-packaging-by-a-combination-of-density-gradient-centrifugation-and-magnetic-activated-cell-sorting
#19
Hee-Jun Chi, Su-Jin Kwak, Seok-Gi Kim, Youn-Young Kim, Ji-Young Park, Chang-Seok Yoo, Il-Hae Park, Hong-Gil Sun, Jae-Won Kim, Kyeong-Ho Lee
OBJECTIVE: This study was carried out to investigate the correlations of the sperm DNA fragmentation index (DFI) with semen parameters and apoptosis, and to investigate the effects of density-gradient centrifugation (DGC) and magnetic-activated cell sorting (MACS) on reducing the proportion of sperm with DNA fragmentation and protamine deficiency. METHODS: Semen analysis and a sperm DNA fragmentation assay were performed to assess the correlations between semen parameters and the DFI in 458 semen samples...
December 2016: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/28077302/neutrophil-adhesion-and-crawling-dynamics-on-liver-sinusoidal-endothelial-cells-under-shear-flow
#20
Hao Yang, Ning Li, Yu Du, Chunfang Tong, Shouqin Lü, Jinrong Hu, Yan Zhang, Mian Long
Neutrophil (polymorphonuclear leukocyte, PMN) recruitment in the liver sinusoid takes place in almost all liver diseases and contributes to pathogen clearance or tissue damage. While PMN rolling unlikely appears in liver sinusoids and Mac-1 or CD44 is assumed to play respective roles during in vivo local or systematic inflammatory stimulation, the regulating mechanisms of PMN adhesion and crawling dynamics are still unclear from those in vivo studies. Here we developed a two-dimensional in vitro sinusoidal model with primary liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) to investigate TNF-α-induced PMN recruitment under shear flow...
February 1, 2017: Experimental Cell Research
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