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https://www.readbyqxmd.com/read/28734805/c-reactive-protein-mediating-immunopathological-lesions-a-potential-treatment-option-for-severe-influenza-a-diseases
#1
Rongbao Gao, Lijie Wang, Tian Bai, Ye Zhang, Hong Bo, Yuelong Shu
Severe influenza diseases with high mortality have been frequently reported, especially in those patients infected with avian influenza A (H5N1, H7N9 or H10N8) or during a pandemic. Respiratory distress, which is attributed to alveolar damage associated with immunopathological lesions, is the most common cause of death. There is a wealth of information on pathogenesis or treatment options. In this study, we showed that high levels of C-reactive protein (CRP) were induced and correlated with complement activation in patients infected with severe influenza A (H5N1, H7N9 or H10N8), and higher levels were induced in fatal patients than in survivors...
July 13, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28734132/high-dimensional-single-cell-mapping-of-cerium-distribution-in-the-lung-immune-microenvironment-of-an-active-smoker
#2
Adeeb H Rahman, Yonit Lavin, Soma Kobayashi, Andrew Leader, Miriam Merad
BACKGROUND: Mass cytometry leverages inductively coupled mass spectrometry to perform high dimensional single cell analyses using antibodies tagged with rare earth isotopes that are considered to be largely absent in biological samples. We have recently noted an unusual exception to this rule while analyzing tissue samples from patients undergoing surgical resection for early stage lung cancer, and here we present a detailed cytometric characterization of cerium in a clinical patient sample...
July 22, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28733045/induction-of-live-cell-phagocytosis-by-a-specific-combination-of-inflammatory-stimuli
#3
Takamasa Ishidome, Takeshi Yoshida, Rikinari Hanayama
Conditions of severe hyper-inflammation can lead to uncontrolled activation of macrophages, and the ensuing phagocytosis of live cells. However, relationships between inflammatory stimuli and uncontrolled phagocytosis of live cells by macrophages are poorly understood. To identify mediators of this process, we established phagocytosis assays of live cells by stimulating macrophages with CpG DNA, interferon-γ, and anti-interleukin-10 receptor antibody. In this model, various cell surface receptors were upregulated on macrophages, and phagocytosis of live cells was induced in a Rac1-dependent manner...
July 13, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28730511/intermediate-molecular-mass-hyaluronan-and-cd44-receptor-interactions-enhance-neutrophil-phagocytosis-and-il-8-production-via-p38-and-erk1-2-mapk-signalling-pathways
#4
Cheng-Hsun Lu, Chia-Huei Lin, Ko-Jen Li, Chieh-Yu Shen, Cheng-Han Wu, Yu-Min Kuo, Ting-Syuan Lin, Chia-Li Yu, Song-Chou Hsieh
CD44 is a common leukocyte adhesion molecule expressed on the surface of various cells. Hyaluronan (HA), the natural ligand of CD44, is a simple repeated disaccharide with variable molecular mass that is widely distributed on cell surfaces and the connective tissue matrix. The binding of small molecular mass HA (SMM-HA, MW < 80 kDa) to CD44 on immune-related cells elicits cell proliferation, differentiation, and cytokine production. However, the effects and molecular basis of intermediate molecular mass HA (IMM-HA, MW ≈ 500 kDa)-CD44 interactions on polymorphonuclear neutrophil (PMN) functions have not been elucidated...
July 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28730104/down-regulation-of-protein-kinase-c-alpha-ezrin-signals-in-light-induced-phagocytic-crisis-of-retinal-pigment-epithelium-cells
#5
Ya-Qiong Zhang, Yong-Gang Fan, Ya-Long Dang, Yan-Li Liu, Hua Liu, Li-Hua Li
AIM: To investigate the roles of PKC-α/ezrin signals in phagocytosis crisis of retinal pigment epithelium (RPE) cells in light damage model. METHODS: Light induced mice RPE injury model was established by continuously irradiating cool white light at different exposure time (0, 4, 8h light intensity: 4.18×10(-6) J/cm(2)). In vitro, human ARPE-19 cells treated with the doses and intensity (1.57×10(-6) J/cm(2)) of laser irradiation. Histology analysis was evaluated by hematoxylin and eosin (HE) staining...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28729628/a-new-approach-for-ratiometric-in-vivo-calcium-imaging-of-microglia
#6
Bianca Brawek, Yajie Liang, Daria Savitska, Kaizhen Li, Natalie Fomin-Thunemann, Yury Kovalchuk, Elizabeta Zirdum, Johan Jakobsson, Olga Garaschuk
Microglia, resident immune cells of the brain, react to the presence of pathogens/danger signals with a large repertoire of functional responses including morphological changes, proliferation, chemotaxis, production/release of cytokines, and phagocytosis. In vitro studies suggest that many of these effector functions are Ca(2+)-dependent, but our knowledge about in vivo Ca(2+) signalling in microglia is rudimentary. This is mostly due to technical reasons, as microglia largely resisted all attempts of in vivo labelling with Ca(2+) indicators...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729539/comparative-proteomic-analysis-of-human-embryonic-stem-cell-derived-and-primary-human-retinal-pigment-epithelium
#7
Heidi Hongisto, Antti Jylhä, Janika Nättinen, Jochen Rieck, Tanja Ilmarinen, Zoltán Veréb, Ulla Aapola, Roger Beuerman, Goran Petrovski, Hannu Uusitalo, Heli Skottman
Human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) provide an unlimited cell source for retinal cell replacement therapies. Clinical trials using hESC-RPE to treat diseases such as age-related macular degeneration (AMD) are currently underway. Human ESC-RPE cells have been thoroughly characterized at the gene level but their protein expression profile has not been studied at larger scale. In this study, proteomic analysis was used to compare hESC-RPE cells differentiated from two independent hESC lines, to primary human RPE (hRPE) using Isobaric tags for relative quantitation (iTRAQ)...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729074/proteomic-analysis-of-the-effects-of-nur77-on-lipopolysaccharide-induced-microglial-activation
#8
Yan Chen, Yuexinzi Jin, Hui Zhan, Jian Chen, Yanting Chen, Hailan Meng, Jiali Jin, Linjie Yu, Xiang Cao, Yun Xu
Microglia are critical components of the immune response in the central nervous system. Our study aims to explore potential role of Nur77 in lipopolysaccharide (LPS)-induced microglial activation. Primary wild-type and Nur77(-/-) microglia were stimulated with LPS and protein extracts were detected via mass spectrometry. Q-PCR and western blotting were performed to validate candidate proteins. A total of 2004 proteins were identified, with 749 and 677 significantly differentially expressed proteins in wild-type and Nur77(-/-) microglia in resting and activated states, respectively...
July 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28728277/-effects-of-pi3k%C3%AE-rhoa-pathway-on-phagocytosis-defect-of-alveolar-macrophages-in-a-mouse-model-of-chronic-obstructive-pulmonary-disease
#9
S T Hu, Q Xia, X L Zeng, H R Bao, X J Liu
Objective: To investigate effects of Phosphoinositide3-Kinases (PI3Kδ)-Ras homolog gene family member A(RhoA) pathway on phagocytosis deficiency of alveolar macrophages (AMs) in a mouse model of chronic obstructive pulmonary disease (COPD). Methods: Twenty mice were exposed to cigarette smoking to establish the COPD model, with 20 mice as the control group. AMs were isolated from lung tissue by discontinuous density gradient centrifugation and then divided into a healthy control group, a COPD group, a healthy IC87114 group and a COPD IC87114 group...
July 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28727817/immunogenicity-of-a-novel-clade-b-hiv-1-vaccine-combination-results-of-phase-1-randomized-placebo-controlled-trial-of-an-hiv-1-gm-csf-expressing-dna-prime-with-a-modified-vaccinia-ankara-vaccine-boost-in-healthy-hiv-1-uninfected-adults
#10
Susan P Buchbinder, Nicole A Grunenberg, Brittany J Sanchez, Kelly E Seaton, Guido Ferrari, M Anthony Moody, Nicole Frahm, David C Montefiori, Christine M Hay, Paul A Goepfert, Lindsey R Baden, Harriet L Robinson, Xuesong Yu, Peter B Gilbert, M Juliana McElrath, Yunda Huang, Georgia D Tomaras
BACKGROUND: A phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity of a DNA prime co-expressing GM-CSF (Dg) followed by different numbers and intervals of modified vaccinia Ankara Boosts (M). Both vaccines produce virus-like particles presenting membrane-bound Env. METHODS: Four US sites randomized 48 participants to receiving 1/10th the DNA dose as DgDgMMM given at 0, 2, 4, 6 and 8 months, or full dose DgDgM_M or DgDgMM_M regimens, given at 0, 2, 4, and 8 months, and 0, 2, 4, 6, and 10 months, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28724897/x-ray-crystallographic-structure-of-a-bacterial-polysialyltransferase-provides-insight-into-the-biosynthesis-of-capsular-polysialic-acid
#11
Christian Lizak, Liam J Worrall, Lars Baumann, Moritz M Pfleiderer, Gesa Volkers, Tianjun Sun, Lyann Sim, Warren Wakarchuk, Stephen G Withers, Natalie C J Strynadka
Polysialic acid (polySia) is a homopolymeric saccharide that is associated with some neuroinvasive pathogens and is found on selective cell types in their eukaryotic host. The presence of a polySia capsule on these bacterial pathogens helps with resistance to phagocytosis, cationic microbial peptides and bactericidal antibody production. The biosynthesis of bacterial polySia is catalysed by a single polysialyltransferase (PST) transferring sialic acid from a nucleotide-activated donor to a lipid-linked acceptor oligosaccharide...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724541/stim1-and-stim2-cooperatively-regulate-mouse-neutrophil-store-operated-calcium-entry-and-cytokine-production
#12
Regina A Clemens, Joshua Chong, Derayvia Grimes, Yongmei Hu, Clifford A Lowell
Neutrophils are key effector cells of the innate immune system. Calcium-dependent signaling pathways initiated by store-operated calcium entry (SOCE) are known to regulate neutrophil activation, however the precise mechanism of this process remains unclear. STIM1 and STIM2 are calcium sensing molecules that link calcium depletion of the endoplasmic reticulum with opening of plasma membrane calcium channels. While a role for STIM1 in neutrophil SOCE and activation has been established, the function of STIM2 is unknown...
July 19, 2017: Blood
https://www.readbyqxmd.com/read/28723692/angiotensin-ii-regulates-dendritic-cells-through-activation-of-nf-%C3%AE%C2%BAb-p65-erk1-2-and-stat1-pathways
#13
Yan Meng, Chen Chen, Yang Liu, Cui Tian, Hui-Hua Li
BACKGROUND: Activation of dendritic cells (DCs) is necessary to initiate immune responses. Angiotensin II (Ang II) has been reported to have a proinflammatory and immunomodulatory function. However, the role of Ang II in regulation of DCs and the underlying mechanisms remain illdefined. METHODS: The effects of Ang II on the proliferation, maturation, phagocytosis, migration, and communication with T cells of DCs were analysed utilizing MTT, flow cytometry, ELISA, transwell assay and mixed lymphocyte culture...
July 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28723556/peroxisome-mediated-metabolism-is-required-for-immune-response-to-microbial-infection
#14
Francesca Di Cara, Avinash Sheshachalam, Nancy E Braverman, Richard A Rachubinski, Andrew J Simmonds
The innate immune response is critical for animal homeostasis and is conserved from invertebrates to vertebrates. This response depends on specialized cells that recognize, internalize, and destroy microbial invaders through phagocytosis. This is coupled to autonomous or non-autonomous cellular signaling via reactive oxygen species (ROS) and cytokine production. Lipids are known signaling factors in this process, as the acute phase response of macrophages is accompanied by systemic lipid changes that help resolve inflammation...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28720729/inhibition-of-inflammasome-dependent-interleukin-1%C3%AE-production-by-streptococcal-nad-glycohydrolase-evidence-for-extracellular-activity
#15
Dóra Hancz, Elsa Westerlund, Benedicte Bastiat-Sempe, Onkar Sharma, Christine Valfridsson, Lena Meyer, John F Love, Maghnus O'Seaghdha, Michael R Wessels, Jenny J Persson
Group A Streptococcus (GAS) is a common human pathogen and the etiologic agent of a large number of diseases ranging from mild, self-limiting infections to invasive life-threatening conditions. Two prominent virulence factors of this bacterium are the genetically and functionally linked pore-forming toxin streptolysin O (SLO) and its cotoxin NAD(+)-glycohydrolase (NADase). Overexpression of these toxins has been linked to increased bacterial virulence and is correlated with invasive GAS disease. NADase can be translocated into host cells by a SLO-dependent mechanism, and cytosolic NADase has been assigned multiple properties such as protection of intracellularly located GAS bacteria and induction of host cell death through energy depletion...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28720697/inhibition-of-complement-c5-protects-against-organ-failure-and-reduces-mortality-in-a-baboon-model-of-escherichia-coli-sepsis
#16
Ravi Shankar Keshari, Robert Silasi, Narcis Ioan Popescu, Maulin Mukeshchandra Patel, Hala Chaaban, Cristina Lupu, K Mark Coggeshall, Tom Eirik Mollnes, Steven J DeMarco, Florea Lupu
Bacterial sepsis triggers robust activation of the complement system with subsequent generation of anaphylatoxins (C3a, C5a) and the terminal complement complex (TCC) that together contribute to organ failure and death. Here we tested the effect of RA101295, a 2-kDa macrocyclic peptide inhibitor of C5 cleavage, using in vitro whole-blood assays and an in vivo baboon model of Escherichia coli sepsis. RA101295 strongly inhibited E. coli-induced complement activation both in vitro and in vivo by blocking the generation of C5a and the soluble form of TCC, sC5b-9...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28717337/effect-of-surface-modification-on-the-in-vitro-protein-adsorption-and-cell-cytotoxicity-of-vinorelbine-nanoparticles
#17
Nandhakumar Sathyamoorthy, Dhanaraju Dasaratha Magharla, Sundar Devendaran Vankayalu
CONTEXT: Nanocarriers possessing long-circulating abilities could take advantage of the pathophysiology of tumor vasculature to achieve spatial placement. To attain such qualities, the drug carriers should possess suitable physicochemical properties such as size and surface hydrophilicity. AIM: The aim of this study was to prepare poly(ε-caprolactone) nanoparticles (NPs) loaded with vinorelbine bitartrate (VB) and to modify its steric properties using polyethylene glycol and poloxamer...
April 2017: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28717031/phagocytic-receptors-activate-syk-and-src-signaling-during-borrelia-burgdorferi-phagocytosis
#18
Tess L Killpack, Maria Ballesteros, Stephen C Bunnell, Alice Bedugnis, Lester Kobzik, Linden T Hu, Tanja Petnicki-Ocwieja
Phagocytosis of the Lyme disease causing pathogen Borrelia burgdorferi has been shown to be important in generating an inflammatory response to the pathogen. As a result, understanding the mechanisms of phagocytosis has been an area of great interest in the field of Lyme disease. Several cell surface receptors that participate in B. burgdorferi phagocytosis have been reported, including scavenger receptor MARCO and integrin α3β1. We sought to define the mechanisms by which these receptors mediated phagocytosis and to identify signaling pathways activated downstream of these receptors upon contact with B...
July 17, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28716912/sialylation-on-o-glycans-protects-platelets-from-clearance-by-liver-kupffer-cells
#19
Yun Li, Jianxin Fu, Yun Ling, Tadayuki Yago, J Michael McDaniel, Jianhua Song, Xia Bai, Yuji Kondo, Yannan Qin, Christopher Hoover, Samuel McGee, Bojing Shao, Zhenghui Liu, Roberto Sonon, Parastoo Azadi, Jamey D Marth, Rodger P McEver, Changgeng Ruan, Lijun Xia
Most platelet membrane proteins are modified by mucin-type core 1-derived glycans (O-glycans). However, the biological importance of O-glycans in platelet clearance is unclear. Here, we generated mice with a hematopoietic cell-specific loss of O-glycans (HC C1galt1(-/-) ). These mice lack O-glycans on platelets and exhibit reduced peripheral platelet numbers. Platelets from HC C1galt1(-/-) mice show reduced levels of α-2,3-linked sialic acids and increased accumulation in the liver relative to wild-type platelets...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716903/autophagy-related-protein-vps34-controls-the-homeostasis-and-function-of-antigen-cross-presenting-cd8%C3%AE-dendritic-cells
#20
Vrajesh V Parekh, Sudheer K Pabbisetty, Lan Wu, Eric Sebzda, Jennifer Martinez, Jianhua Zhang, Luc Van Kaer
The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34-deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
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