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https://www.readbyqxmd.com/read/28539873/pharmacological-stimulation-of-phagocytosis-enhances-amyloid-plaque-clearance-evidence-from-a-transgenic-mouse-model-of-attr-neuropathy
#1
Eleni Fella, Kleitos Sokratous, Revekka Papacharalambous, Kyriacos Kyriacou, Joy Phillips, Sam Sanderson, Elena Panayiotou, Theodoros Kyriakides
Hereditary ATTR V30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by deposition of aberrant transthyretin (TTR). Immunohistochemical examination of sural nerve biopsies in patients with amyloidotic neuropathy show co-aggregation of TTR with several proteins; including apolipoprotein E, serum amyloid P and components of the complement cascade. Complement activation and macrophages are increasingly recognized to play a crucial role in amyloidogenesis at the tissue bed level...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28539427/tlr-induced-murine-dendritic-cell-dc-activation-requires-dc-intrinsic-complement
#2
Joong-Hyuk Sheen, Michael G Strainic, Jinbo Liu, Weijia Zhang, Zhengzi Yi, M Edward Medof, Peter S Heeger
Induction of proinflammatory T cell immunity is augmented by innate dendritic cell (DC) maturation commonly initiated by TLR signaling. We demonstrate that ligation of TLR3, TLR4, and TLR9 induces murine DC production of complement components and local production of the anaphylatoxin C5a. In vitro, ex vivo, and in vivo analyses show that TLR-induced DC maturation, as assessed by surface phenotype, expression profiling by gene array, and functional ability to stimulate T cell responses, requires autocrine C3a receptor and C5a receptor (C3ar1/C5ar1) signaling...
May 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28529998/complement-c5a-receptor-is-the-key-initiator-of-neutrophil-adhesion-igniting-immune-complex-induced-arthritis
#3
Yoshishige Miyabe, Chie Miyabe, Thomas T Murooka, Edward Y Kim, Gail A Newton, Nancy D Kim, Bodduluri Haribabu, Francis W Luscinskas, Thorsten R Mempel, Andrew D Luster
The deposition of immune complexes (IC) in tissues induces a "type III hypersensitivity" that results in tissue damage and underlies the pathogenesis of many autoimmune diseases. The neutrophil is the first immune cell recruited into sites of IC deposition and plays a critical role in shaping the overall tissue response. However, the mechanism by which IC initiate and propagate neutrophil infiltration into tissue is not known. Here, using intravital multiphoton joint imaging of IC-induced arthritis in live mice, we found that the complement C5a receptor (C5aR) was the key initiator of neutrophil adhesion on joint endothelium...
January 2017: Science Immunology
https://www.readbyqxmd.com/read/28527850/complement-activation-by-pulp-capping-materials-plays-a-significant-role-in-both-inflammatory-and-pulp-stem-cells-recruitment
#4
Thomas Giraud, Pierre Rufas, Fanny Chmilewsky, Charlotte Rombouts, Jacques Dejou, Charlotte Jeanneau, Imad About
INTRODUCTION: The role of complement, especially through the C5a fragment, is well-known for the initiation of inflammation. Its involvement in regeneration has been shown more recently by the recruitment of mesenchymal stem cells. C5a can be produced locally by the pulp fibroblasts in response to injury or infection. This work aims to investigate the effect of different pulp capping biomaterials on complement activation and its possible influence on inflammatory and pulp stem cell recruitment...
May 17, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28523567/peripheral-viral-challenge-triggers-hippocampal-production-of-inflammatory-proteins
#5
Tiffany Petrisko, Gregory Konat
Peripheral viral infections increase seizure propensity and intensity in susceptible individuals. We have modeled this comorbidity by demonstrating that intraperitoneal (ip) injection of the conventional viral mimetic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to seizures induced by kainic acid (KA). At the molecular level, the hippocampus, which is the ictal site of KA-induced seizures, exhibits upregulated expression of messages encoding several inflammatory genes. Here, we profiled temporal expression of these genes at the protein level...
May 18, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28516949/paroxysmal-nocturnal-haemoglobinuria
#6
REVIEW
Anita Hill, Amy E DeZern, Taroh Kinoshita, Robert A Brodsky
Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell (HSC) disease that presents with haemolytic anaemia, thrombosis and smooth muscle dystonias, as well as bone marrow failure in some cases. PNH is caused by somatic mutations in PIGA (which encodes phosphatidylinositol N-acetylglucosaminyltransferase subunit A) in one or more HSC clones. The gene product of PIGA is required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; thus, PIGA mutations lead to a deficiency of GPI-anchored proteins, such as complement decay-accelerating factor (also known as CD55) and CD59 glycoprotein (CD59), which are both complement inhibitors...
May 18, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28504607/innate-inflammatory-gene-expression-profiling-in-potential-brain-dead-donors-detailed-investigation-of-the-effect-of-common-corticosteroid-therapy
#7
Reza Gholamnezhadjafari, Nader Tajik, Reza Falak, Reza Aflatoonian, Sanaz Dehghan, Abbas Rezaei
Our study aimed to assess the influence of common methylprednisolone therapy on innate inflammatory factors in potential brain-dead organ donors (BDDs). The study groups consisted of 50 potential BDDs who received 15 mg/kg/d methylprednisolone and 25 live organ donors (LDs) as control group. Innate immunity gene expression profiling was performed by RT-PCR array. Soluble serum cytokines and chemokines, complement components, heat shock protein 70 (HSP70) and high mobility group box-1 (HMGB1) were measured by ELISA...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28490576/complement-c5a-functions-as-a-master-switch-for-the-ph-balance-in-neutrophils-exerting-fundamental-immunometabolic-effects
#8
Stephanie Denk, Miriam D Neher, David A C Messerer, Rebecca Wiegner, Bo Nilsson, Daniel Rittirsch, Kristina Nilsson-Ekdahl, Sebastian Weckbach, Anita Ignatius, Miriam Kalbitz, Florian Gebhard, Manfred E Weiss, Josef Vogt, Peter Radermacher, Jörg Köhl, John D Lambris, Markus S Huber-Lang
During sepsis, excessive activation of the complement system with generation of the anaphylatoxin C5a results in profound disturbances in crucial neutrophil functions. Moreover, because neutrophil activity is highly dependent on intracellular pH (pHi), we propose a direct mechanistic link between complement activation and neutrophil pHi In this article, we demonstrate that in vitro exposure of human neutrophils to C5a significantly increased pHi by selective activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated intracellular alkalinization was dependent on C5aR1, intracellular calcium, protein kinase C, and calmodulin, and downstream signaling regulated the release of antibacterial myeloperoxidase and lactoferrin...
May 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28477014/anti-complement-component-5-antibody-targeting-mg4-domain-inhibits-choroidal-neovascularization
#9
Dong Hyun Jo, Jin Hyoung Kim, Wonjun Yang, Hyori Kim, Shinjae Chang, Dongjo Kim, Minseok Chang, Kihwang Lee, Junho Chung, Jeong Hun Kim
Age-related macular degeneration (AMD) is one of the main causes of visual impairment in adults. Visual deterioration is more prominent in neovascular AMD with choroidal neovascularization (CNV). Clinical and postmortem studies suggested that complement system activation might induce CNV. In this study, we demonstrated that an anti-mouse complement component 5 (C5) antibody targeting MG4 domain of β chain effectively inhibited CNV which was induced by laser photocoagulation in mice. The targeted epitope of this anti-C5 antibody was different from that of currently utilized anti-C5 antibody (eculizumab) in the MG7 domain in which a single nucleotide polymorphism (R885H/C) results in poor response to eculizumab...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28474458/accuracy-of-complement-activation-product-levels-to-detect-infected-pleural-effusion-in-rats
#10
Guilherme E Peterson, Samanta S Silva, Sérgio L Amantéa, Patrícia Miorelli, Paulo Sanches, Jane Kulczynski, Eliane Roesch, José Carlos Fraga
BACKGROUND: Pleural empyema is a well-known complication of pneumonia. If treatment is delayed, empyema may increase morbidity and mortality in affected patients. Therefore, the identification of empyema biomarkers in parapneumonic pleural effusion is desirable. Previous research has suggested complement activation products as candidate empyema markers. OBJECTIVE: To compare the levels of complement activation products C3a, C5a, and C5b9 in pleural effusion induced by Staphylococcus aureus (SA), Streptococcus pneumoniae (SP), or turpentine (control)...
May 5, 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28457935/nf-%C3%AE%C2%BAb-inhibitors-that-prevent-foam-cell-formation-and-atherosclerotic-plaque-accumulation
#11
Jesse D Plotkin, Michael G Elias, Anthony L Dellinger, Christopher L Kepley
The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. Thus, it was hypothesized that FD could inhibit the transformation process underlying foam cell formation. Fullerene derivatives inhibited the phorbol myristic acid/oxidized low-density lipoprotein-induced differentiation of macrophages into foam cells as determined by lipid staining and morphology...
April 27, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28455369/complement-c5ar1-signaling-promotes-polarization-and-proliferation-of-embryonic-neural-progenitor-cells-through-pkc%C3%AE
#12
Liam G Coulthard, Owen A Hawksworth, Rui Li, Anushree Balachandran, John D Lee, Farshid Sepehrband, Nyoman Kurniawan, Angela Jeanes, David G Simmons, Ernst Wolvetang, Trent M Woodruff
The complement system, typically associated with innate immunity, is emerging as a key controller of non-immune systems including in development, with recent studies linking complement mutations with neurodevelopmental disease. A key effector of the complement response is the activation fragment C5a which, through its receptor C5aR1, is a potent driver of inflammation. Surprisingly, C5aR1 is also expressed during early mammalian embryogenesis, however no clearly defined function is ascribed to C5aR1 in development...
April 28, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28443070/crystal-structure-of-glyceraldehyde-3-phosphate-dehydrogenase-from-the-gram-positive-bacterial-pathogen-a-vaginae-an-immunoevasive-factor-that-interacts-with-the-human-c5a-anaphylatoxin
#13
Javier Querol-García, Francisco J Fernández, Ana V Marin, Sara Gómez, Daniel Fullà, Cecilia Melchor-Tafur, Virginia Franco-Hidalgo, Sebastián Albertí, Jordi Juanhuix, Santiago Rodríguez de Córdoba, José R Regueiro, M Cristina Vega
The Gram-positive anaerobic human pathogenic bacterium Atopobium vaginae causes most diagnosed cases of bacterial vaginosis as well as opportunistic infections in immunocompromised patients. In addition to its well-established role in carbohydrate metabolism, D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Streptococcus pyogenes and S. pneumoniae have been reported to act as extracellular virulence factors during streptococcal infections. Here, we report the crystal structure of GAPDH from A. vaginae (AvGAPDH) at 2...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28442885/complement-c5a-receptor-knockout-has-diminished-light-induced-microglia-macrophage-retinal-migration
#14
Delu Song, Michael E Sulewski, Chenguang Wang, Jiantao Song, Rupak Bhuyan, Jacob Sterling, Esther Clark, Wen-Chao Song, Joshua L Dunaief
PURPOSE: The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. METHODS: We assessed the effect of anaphylatoxin C3a receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced migration of microglia/macrophages into the mouse outer retina via immunofluorescence and real-time quantitative PCR...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28429668/the-role-of-mitochondria-associated-reactive-oxygen-species-in-the-amyloid-%C3%AE-induced-production-of-angiogenic-factors-by-arpe-19-cells
#15
L Wu, X Tan, L Liang, H Yu, C Wang, D Zhang, A Kijlstra, P Yang
OBJECTIVE: This study aimed to investigate the mechanisms whereby Amyloid-beta (Aβ) induces the production of angiogenic factors by a human retinal pigment epithelial cell line (ARPE-19) cells. METHODS: ARPE-19 cells obtained from the American Type Culture Collection (ATCC) were utilized in this study. The expression level of vascular endothelial growth factor (VEGF), Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and complement activation fragments C3a and C5a were measured by Real-time quantitative PCR (RT-PCR) and Enzyme-linked immunosorbent assay (ELISA)...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28420473/-the-study-of-serum-complements-and-proinflammatory-cytokines-in-sepsis-rats
#16
Ping Sun, Dongqiang Wang, Chunlei Zhou, Zhiqin Tang, Wei Liu, Hong Mu
OBJECTIVE: To observe the changes of serum complements and proinflammatory cytokines in rats with sepsis, and to explore the possible mechanism. METHODS: 120 healthy male Wistar rats were randomly divided into three groups: normal control group (n = 15), sham operation group (n = 15) and sepsis group [cecum ligation and puncture (CLP) operation, n = 90]. The sepsis rats were sacrificed on 24, 48 and 72 hours after modeling. The level of serum complements (C5, C5a) and cytokines tumor necrosis factor-α (TNF-α), interleukin (IL-1, IL-6), high mobility group box 1 (HMGB1), macrophage migration inhibitory factor (MIF) were detected by enzyme linked immunosorbent assay (ELISA)...
April 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28415521/effect-of-halloysite-nanotubes-on-the-structure-and-function-of-important-multiple-blood-components
#17
Keke Wu, Ru Feng, Yanpeng Jiao, Changren Zhou
Many researchers have investigated the application of halloysite nanotubes (HNTs) in biomedicine, because of their special nanoscale hollow tubular structure. Although the cytocompatibility of HNTs has been studied, their blood compatibility has not been systematically investigated. In this work, the effect of HNTs on the structure and function of different blood components has been studied, including the morphology and hemolysis of red blood cells (RBCs). Based on scanning electron microscopy (SEM) observations, optical density test and flow cytometry analysis, we found that HNTs can affect the morphology and membrane integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28400446/randomized-trial-of-c5a-receptor-inhibitor-avacopan-in-anca-associated-vasculitis
#18
David R W Jayne, Annette N Bruchfeld, Lorraine Harper, Matthias Schaier, Michael C Venning, Patrick Hamilton, Volker Burst, Franziska Grundmann, Michel Jadoul, István Szombati, Vladimír Tesař, Mårten Segelmark, Antonia Potarca, Thomas J Schall, Pirow Bekker
Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone...
April 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28397467/increase-of-c3a-is-associated-with-hemorrhagic-propensity-in-patients-with-immune-thrombocytopenia
#19
Jian Ge, Lihong Wang, Jing Li, Yan Hu, Qianfei Xu, Yang Chen, Ruiqin Hou, Min Ruan, Ruixiang Xia, Qingshu Zeng
BACKGROUND: Complement activation is critically involved in multiple autoimmune diseases. Immune thrombocytopenia (ITP) is a hemorrhagic condition with enhanced platelet clearance caused by antiplatelet autoantibodies. However, the roles of complements C3a, C5a, and soluble C5b-9 (sC5b-9) in the hemorrhage of ITP remain unknown. METHODS: Plasma C3a, C5a, and sC5b-9 levels in ITP patients were measured by enzyme-linked immunosorbent assay (ELISA). Antiplatelet autoantibodies (anti-GPIIb/IIIa and anti-GPIbα) were evaluated by modified monoclonal antibody immobilization of platelet antigen (MAIPA) assay...
April 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28396344/critical-role-for-complement-receptor-c5ar2-in-the-pathogenesis-of-renal-ischemia-reperfusion-injury
#20
Felix Poppelaars, Maaike B van Werkhoven, Juha Kotimaa, Zwanida J Veldhuis, Albertina Ausema, Stefan G M Broeren, Jeffrey Damman, Julia C Hempel, Henri G D Leuvenink, Mohamed R Daha, Willem J van Son, Cees van Kooten, Ronald P van Os, Jan-Luuk Hillebrands, Marc A Seelen
The complement system, and specifically C5a, is involved in renal ischemia-reperfusion (IR) injury. The 2 receptors for complement anaphylatoxin C5a (C5aR1 and C5aR2) are expressed on leukocytes as well as on renal epithelium. Extensive evidence shows that C5aR1 inhibition protects kidneys from IR injury; however, the role of C5aR2 in IR injury is less clear as initial studies proposed the hypothesis that C5aR2 functions as a decoy receptor. By Using wild-type, C5aR1(-/-), and C5aR2(-/-) mice in a model of renal IR injury, we found that a deficiency of either of these receptors protected mice from renal IR injury...
April 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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