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Complement receptor 3

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https://www.readbyqxmd.com/read/28314853/activation-of-the-orphan-g-protein-coupled-receptor-gpr27-by-surrogate-ligands-promotes-%C3%AE-arrestin-2-recruitment
#1
Nadine Dupuis, Celine Laschet, Delphine Franssen, Martyna Szpakowska, Julie Gilissen, Pierre Geubelle, Arvind Soni, Anne-Simone Parent, Bernard Pirotte, Andy Chevigne, Jean-Claude Twizere, Julien Hanson
G protein-coupled receptors are the most important drug targets for human diseases. An important number of them remain devoid of confirmed ligands. GPR27 is one of these orphan receptors, characterized by a high level of conservation among vertebrates and a predominant expression in the central nervous system. In addition, it has recently been linked to insulin secretion. However, the absence of endogenous or surrogate ligands for GPR27 complicates the examination of its biological function. Our aim was to validate GPR27 signaling pathways and therefore we sought to screen a diversity oriented synthesis library to identify GPR27-specific surrogate agonists...
March 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28303661/immunological-and-physiological-observations-in-baboons-with-life-supporting-genetically-engineered-pig-kidney-grafts
#2
Hayato Iwase, Hidetaka Hara, Mohamed Ezzelarab, Tao Li, Zhongqiang Zhang, Bingsi Gao, Hong Liu, Cassandra Long, Yi Wang, Amy Cassano, Edwin Klein, Carol Phelps, David Ayares, Abhinav Humar, Martin Wijkstrom, David K C Cooper
BACKGROUND: Genetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310 days, but graft survival >30 days has been unusual until recently. METHODS: Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein...
March 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28298456/microglial-complement-receptor-3-regulates-brain-a%C3%AE-levels-through-secreted-proteolytic-activity
#3
Eva Czirr, Nicholas A Castello, Kira I Mosher, Joseph M Castellano, Izumi V Hinkson, Kurt M Lucin, Bernat Baeza-Raja, Jae Kyu Ryu, Lulin Li, Sasha N Farina, Nadia P Belichenko, Frank M Longo, Katerina Akassoglou, Markus Britschgi, John R Cirrito, Tony Wyss-Coray
Recent genetic evidence supports a link between microglia and the complement system in Alzheimer's disease (AD). In this study, we uncovered a novel role for the microglial complement receptor 3 (CR3) in the regulation of soluble β-amyloid (Aβ) clearance independent of phagocytosis. Unexpectedly, ablation of CR3 in human amyloid precursor protein-transgenic mice results in decreased, rather than increased, Aβ accumulation. In line with these findings, cultured microglia lacking CR3 are more efficient than wild-type cells at degrading extracellular Aβ by secreting enzymatic factors, including tissue plasminogen activator...
March 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28289553/%C3%AE-gal-nanoparticles-in-wound-and-burn-healing-acceleration
#4
REVIEW
Uri Galili
Significance: Rapid recruitment and activation of macrophages may accelerate wound healing. Such accelerated healing was observed in wounds and burns of experimental animals treated with α-gal nanoparticles. Recent Advances: α-Gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). α-Gal nanoparticles applied to wounds bind anti-Gal (the most abundant antibody in humans) and generate chemotactic complement peptides, which rapidly recruit macrophages. Fc/Fc receptor interaction between anti-Gal coating the α-gal nanoparticles and recruited macrophages activates macrophages to produce cytokines that accelerate healing...
March 1, 2017: Advances in Wound Care
https://www.readbyqxmd.com/read/28285325/mglu1-receptor-as-a-drug-target-for-treatment-of-substance-use-disorders-time-to-gather-stones-together
#5
REVIEW
Olga A Dravolina, Edwin Zvartau, Wojciech Danysz, Anton Y Bespalov
Modulation of the mGlu1 receptor was repeatedly shown to inhibit various phenomena associated with exposure to abused drugs. Efficacy in preclinical models was observed with both positive and negative allosteric modulators (PAMs and NAMs, respectively) using essentially non-overlapping sets of experimental methods. Taken together, these data indicate that the mGlu1 receptor certainly plays a significant role in the plasticity triggered by the exposure to abused drugs and is involved in the maintenance of drug-seeking and drug-taking behaviors...
March 11, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28285017/effects-of-the-aryl-hydrocarbon-receptor-agonist-3-methylcholanthrene-on-the-17%C3%AE-estradiol-regulated-mrna-transcriptome-of-the-rat-uterus
#6
Janina Helle, Annekathrin M Keiler, Oliver Zierau, Peggy Dörfelt, Günter Vollmer, Leane Lehmann, Sridar V Chittur, Martin Tenniswood, JoEllen Welsh, Georg Kretzschmar
Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion of organic compounds, abundant in exhaust fumes and cigarette smoke. They act by binding to the aryl hydrocarbon receptor (AHR) which induces expression of phase 1 and phase 2 enzymes in the liver. PAH induced AHR activation may also lead to adverse effects by modulating other pathways, for example estrogen receptor (ER) signaling in the female reproductive tract. We have investigated the effects of the PAH 3-methylcholanthrene (3-MC) on 17β-estradiol (E2) dependent signaling in the uterus of ovariectomized rats to characterize the cross talk between AHR and ER on an mRNA transcriptome wide scale...
March 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28284604/identification-of-the-ferric-iron-utilization-gene-b739_1208-and-its-role-in-the-virulence-of-r-anatipestifer-ch-1
#7
MengYi Wang, PengYun Zhang, DeKang Zhu, MingShu Wang, RenYong Jia, Shun Chen, KunFeng Sun, Qiao Yang, Ying Wu, XiaoYue Chen, Francis Biville, AnChun Cheng, MaFeng Liu
Riemerella anatipestifer is an important bacterial pathogen in ducks and causes heavy economic losses in the duck industry. However, the pathogensis of this bacterium is poorly understood. In this study, a putative outer membrane hemin receptor gene B739_1208 in R. anatipestifer CH-1 was deleted to determine the relationship between iron uptake and virulence. The R. anatipestifer CH-1ΔB739_1208 mutants grew significantly more slowly than the wild-type bacteria in TSB liquid medium. Further characterization revealed that the R...
March 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28283064/complement-component-3-adapts-the-cerebrospinal-fluid-for-leptomeningeal-metastasis
#8
Adrienne Boire, Yilong Zou, Jason Shieh, Danilo G Macalinao, Elena Pentsova, Joan Massagué
We molecularly dissected leptomeningeal metastasis, or spread of cancer to the cerebrospinal fluid (CSF), which is a frequent and fatal condition mediated by unknown mechanisms. We selected lung and breast cancer cell lines for the ability to infiltrate and grow in CSF, a remarkably acellular, mitogen-poor metastasis microenvironment. Complement component 3 (C3) was upregulated in four leptomeningeal metastatic models and proved necessary for cancer growth within the leptomeningeal space. In human disease, cancer cells within the CSF produced C3 in correlation with clinical course...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28279791/methionine-hydroxy-analogue-improves-intestinal-immunological-and-physical-barrier-function-in-young-grass-carp-ctenopharyngodon-idella
#9
Fei-Yu Pan, Pei Wu, Lin Feng, Wei-Dan Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou, Yang Liu
This study was conducted to test the hypothesis that methionine hydroxy analogue (MHA) enhances the defense against enteritis occurrence via improving intestinal barrier function in fish. After 630 young grass carp (Ctenopharyngodon idella) (259.70 ± 0.47 g) fed six graded levels of MHA (0, 2.4, 4.4, 6.4, 8.5 and 10.5 g/kg diet) and one dl-methionine group (6.4 g/kg diet) for 8 weeks. At the end of feeding trial, 15 fish from each treatment were challenged with Aeromonas hydrophila for 14 days. The results indicated that optimal MHA enhanced the capacity of fish against enteritis emergence, which might be related to the positive effects of MHA on intestinal immunological and physical barrier function in fish...
March 6, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28265373/a-generalized-quantitative-antibody-homeostasis-model-regulation-of-b-cell-development-by-bcr-saturation-and-novel-insights-into-bone-marrow-function
#10
József Prechl
In a pair of articles, we present a generalized quantitative model for the homeostatic function of clonal humoral immune system. In this first paper, we describe the cycles of B-cell expansion and differentiation driven by B-cell receptor engagement. The fate of a B cell is determined by the signals it receives via its antigen receptor at any point of its lifetime. We express BCR engagement as a function of apparent affinity and free antigen concentration, using the range of 10(-14)-10(-3) M for both factors...
February 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28263819/cortisol-plays-a-role-in-the-high-environmental-ammonia-associated-suppression-of-the-immune-response-in-zebrafish
#11
A F Gonçalves, J V Neves, J Coimbra, P Rodrigues, M M Vijayan, J M Wilson
Exposure to high environmental ammonia (HEA) levels increases the vulnerability of fishes to parasitic, viral and bacterial diseases. We tested the hypothesis that elevated plasma cortisol levels play a role in the HEA-mediated immunosuppression in fishes. To this end, we tested the effect of exogenous cortisol treatment on the lipopolysaccharide (LPS)-induced immune response in zebrafish (Danio rerio). Also, to test whether glucocorticoid receptor (GR) signaling is involved in HEA-mediated immunosuppression, zebrafish were treated with mifepristone, a GR antagonist, and the LPS-induced immune response assessed after HEA exposure...
March 2, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28261486/combined-inhibition-of-c5-and-cd14-efficiently-attenuated-the-inflammatory-response-in-a-porcine-model-of-meningococcal-sepsis
#12
Bernt C Hellerud, Hilde L Orrem, Knut Dybwik, Søren E Pischke, Andreas Baratt-Due, Albert Castellheim, Hilde Fure, Grethe Bergseth, Dorte Christiansen, Miles A Nunn, Terje Espevik, Corinna Lau, Petter Brandtzæg, Erik W Nielsen, Tom E Mollnes
BACKGROUND: Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key molecules of innate immunity, complement component C5, and co-receptor CD14 in the Toll-like receptor system, on the inflammatory response in meningococcal sepsis. METHODS: Meningococcal sepsis was simulated by continuous intravenous infusion of an escalating dose of heat-inactivated Neisseria meningitidis administered over 3 h...
2017: Journal of Intensive Care
https://www.readbyqxmd.com/read/28258200/endogenous-natural-complement-inhibitor-regulates-cardiac-development
#13
Simon A Mortensen, Louise L Skov, Kasper Kjaer-Sorensen, Annette G Hansen, Søren Hansen, Frederik Dagnæs-Hansen, Jens C Jensenius, Claus Oxvig, Steffen Thiel, Søren E Degn
Congenital heart defects are a major cause of perinatal mortality and morbidity, affecting >1% of all live births in the Western world, yet a large fraction of such defects have an unknown etiology. Recent studies demonstrated surprising dual roles for immune-related molecules and their effector mechanisms during fetal development and adult homeostasis. In this article, we describe the function of an endogenous complement inhibitor, mannan-binding lectin (MBL)-associated protein (MAp)44, in regulating the composition of a serine protease-pattern recognition receptor complex, MBL-associated serine protease (MASP)-3/collectin-L1/K1 hetero-oligomer, which impacts cardiac neural crest cell migration...
March 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28237943/kinome-profiling-identifies-druggable-targets-for-novel-hcmv-antivirals
#14
Kyle C Arend, Erik M Lenarcic, Heather A Vincent, Naim Rashid, Eric Lazear, Ian M McDonald, Thomas S K Gilbert, Michael P East, Laura E Herring, Gary L Johnson, Lee Graves, Nathaniel J Moorman
Human cytomegalovirus (HCMV) is a significant cause of disease in immunecompromised adults and immune naive newborns. No vaccine exists to prevent HCMV infection, and current antiviral therapies have toxic side effects that limit the duration and intensity of their use. There is thus an urgent need for new strategies to treat HCMV infection. Repurposing existing drugs as antivirals is an attractive approach to limit the time and cost of new antiviral drug development. Virus-induced changes in infected cells are often driven by changes in cellular kinase activity, which led us to hypothesize that defining the complement of kinases (the kinome), whose abundance or expression is altered during infection would identify existing kinase inhibitors that could be repurposed as new antivirals...
February 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28228690/human-cytomegalovirus-interleukin-10-enhances-matrigel-invasion-of-mda-mb-231-breast-cancer-cells
#15
Cendy A Valle Oseguera, Juliet V Spencer
BACKGROUND: While some risk factors for breast cancer are well-known, the influence of other factors, particularly virus infection, remains unclear. Human cytomegalovirus (HCMV) is widespread in the general population, and both molecular and epidemiological evidence has indicated links between HCMV and breast cancer. The HCMV protein cmvIL-10 is a potent suppressor of immune function that has also been shown to promote proliferation and migration of breast cancer cells. In this study, the impact of cmvIL-10 on tumor cell invasion through a simulated basement membrane was investigated...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28218976/differential-expression-of-innate-immune-response-genes-in-clinical-phases-of-chronic-hepatitis-b-infection
#16
Sara Romani, Seyed Masoud Hosseini, Seyed Reza Mohebbi, Andre Boonstra, Afsaneh Sharifian
We investigated innate immune gene expression in clinical phases of Chronic Hepatitis B infection, including immune tolerant (IT); immune active (IA); inactive carrier (IC); and hepatitis B e antigen (HBeAg)-negative phases, as well as healthy controls. Expression levels of interferon types I, II, and III, their receptor subunits, IRFs, TLRs and other IFN-induced genes in peripheral blood mononuclear cells were compared.Forty HBsAg-positive treatment-naïve subjects without co-infection with HIV, HCV or HDV were enrolled...
February 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28195315/genetic-testing-facilitates-prepubertal-diagnosis-of-congenital-hypogonadotropic-hypogonadism
#17
Cheng Xu, Mariarosaria Lang-Muritano, Franziska Phan-Hug, Andrew A Dwyer, Gerasimos P Sykiotis, Daniele Cassatella, James Acierno, Moosa Mohammadi, Nelly Pitteloud
Neonatal micropenis and cryptorchidism raise the suspicion of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder caused by GnRH deficiency. Low plasma testosterone levels and low gonadotropins during minipuberty provide a clinical diagnostic clue, yet these tests are seldomly performed in general practice. We report a male neonate with no family history of reproductive disorders who was born with micropenis and cryptorchidism. Hormonal testing at age 2.5 months showed low testosterone (0...
February 14, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28191010/role-of-dietary-metabolites-in-regulating-the-host-immune-response-in-gastrointestinal-disease
#18
REVIEW
Mohamad El-Zaatari, John Y Kao
The host immune response to gastrointestinal (GI) infections, hypersensitivity reactions, or GI cancers comprises numerous pathways that elicit responses on different host cells. Some of these include (1) the stimulation of mast cells via their IgE receptor, (2) the production of antibodies leading to antibody-mediated cytotoxic T/natural killer cell killing, (3) the activation of the complement pathway, and (4) the activation of the adaptive immune response via antigen-presenting cell, T cell, and B cell interactions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28187163/enhanced-survival-of-leishmania-major-in-neutrophil-granulocytes-in-the-presence-of-apoptotic-cells
#19
Natallia Salei, Lars Hellberg, Jörg Köhl, Tamás Laskay
Neutrophil granulocytes are the first leukocytes that encounter and phagocytose Leishmania major (L. major) parasites in the infected skin. The parasites can nonetheless survive within neutrophils. However, the mechanisms enabling the survival of Leishmania within neutrophils are still elusive. Previous findings indicated that human neutrophils can engulf apoptotic cells. Since apoptotic neutrophils are abundant in infected tissues, we hypothesized that the uptake of apoptotic cells results in diminished anti-leishmanial activity and, consequently, contributes to enhanced survival of the parasites at the site of infection...
2017: PloS One
https://www.readbyqxmd.com/read/28128456/pharmacological-inhibition-of-complement-c5a-c5a1-receptor-signalling-ameliorates-disease-pathology-in-the-hsod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#20
John D Lee, Vinod Kumar, Jenny N T Fung, Marc J Ruitenberg, Peter G Noakes, Trent M Woodruff
BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing motor neuron disease without effective treatment. The complement system is up-regulated in ALS, with recent studies indicating that the activation product C5a accelerates disease progression via the C5a1 receptor (C5aR1). We therefore examined the therapeutic effect of C5a1 receptor antagonism in hSOD1(G93A) mice, the most widely used preclinical model of ALS. EXPERIMENTAL APPROACH: The selective and orally active C5a1 receptor antagonist, PMX205, was administered to hSOD1(G93A) mice in drinking water, both pre- and post-disease onset...
April 2017: British Journal of Pharmacology
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