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Complement alternative pathway

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https://www.readbyqxmd.com/read/29150548/defense-against-reactive-carbonyl-species-involves-at-least-three-subcellular-compartments-where-individual-components-of-the-system-respond-to-cellular-sugar-status
#1
Jessica Schmitz, Isabell C Dittmar, Jörn D Brockmann, Marc Schmidt, Meike Hüdig, Alessandro W Rossoni, Veronica G Maurino
Methylglyoxal (MGO) and glyoxal (GO) are toxic reactive carbonyl species generated as by-products of glycolysis. The pre-emption pathway for detoxification of these products, the glyoxalase (GLX) system, involves two consecutive reactions catalyzed by GLXI and GLXII. In Arabidopsis thaliana, the GLX system is encoded by three homologs of GLXI and three homologs of GLXII, from which several predicted GLXI and GLXII isoforms can be derived through alternative splicing. We identified the physiologically relevant splice forms using sequencing data and demonstrated that the resulting isoforms have different subcellular localizations...
November 17, 2017: Plant Cell
https://www.readbyqxmd.com/read/29141676/platelets-are-activated-in-anca-associated-vasculitis-via-thrombin-pars-pathway-and-can-activate-the-alternative-complement-pathway
#2
Di Miao, Dan-Yang Li, Min Chen, Ming-Hui Zhao
BACKGROUND: In this study, we investigated the mechanism of platelet activation in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), as well as the activation of the alternative complement pathway by platelets in AAV. METHODS: CD62P and platelet-leukocyte aggregates in AAV patients were tested by flow cytometry. Platelets were stimulated by plasma from active AAV patients. The effect of the thrombin-protease-activated receptors (PARs) pathway was evaluated by blocking thrombin or PAR1 antagonists...
November 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29133887/a-complementary-scale-of-biased-agonism-for-agonists-with-differing-maximal-responses
#3
Javier Burgueño, Marta Pujol, Xavier Monroy, David Roche, Maria Jose Varela, Manuel Merlos, Jesús Giraldo
Compelling data in the literature from the recent years leave no doubt about the pluridimensional nature of G protein-coupled receptor function and the fact that some ligands can couple with different efficacies to the multiple pathways that a receptor can signal through, a phenomenon most commonly known as functional selectivity or biased agonism. Nowadays, transduction coefficients (log(τ/KA)), based on the Black and Leff operational model of agonism, are widely used to calculate bias. Nevertheless, combining both affinity and efficacy in a single parameter can result in compounds showing a defined calculated bias of one pathway over other though displaying varying experimental bias preferences...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29128668/inhibition-of-the-complement-system-by-saliva-of-anopheles-nyssorhynchus-aquasalis
#4
Antonio Ferreira Mendes-Sousa, Vladimir Fazito Vale, Daniel Costa Queiroz, Adalberto Alves Pereira-Filho, Naylene Carvalho Sales da Silva, Leonardo Barbosa Koerich, Luciano Andrade Moreira, Marcos Horácio Pereira, Maurício Roberto Sant'Anna, Ricardo Nascimento Araújo, John Andersen, Jesus Gilberto Valenzuela, Nelder Figueiredo Gontijo
Anopheline mosquitoes are vectors of malaria parasites. Their saliva contains anti-hemostatic and immune-modulator molecules that favor blood feeding and parasite transmission. In this study, we describe the inhibition of the alternative pathway of the complement system (AP) by Anopheles aquasalis salivary gland extracts (SGE). According to our results, the inhibitor present in SGE acts on the initial step of the AP blocking deposition of C3b on the activation surfaces. Properdin, which is a positive regulatory molecule of the AP, binds to SGE...
November 8, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29126055/estrogen-responsive-gene-networks-in-the-teleost-liver-what-are-the-key-molecular-indicators
#5
April Feswick, Kelly R Munkittrick, Christopher J Martyniuk
An overarching goal of environmental genomics is to leverage sensitive suites of markers that are robust and reliable to assess biological responses in a range of species inhabiting variable environments. The objective of this study was to identify core groups of transcripts and molecular signaling pathways that respond to 17alpha-ethylinestadiol (EE2), a ubiquitous estrogenic contaminant, using transcriptome datasets generated from six independent laboratories. We sought to determine which biomarkers and gene networks were those most robust and reliably detected in multiple laboratories...
October 31, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29114042/deletion-variants-of-cfhr1-and-cfhr3-associate-with-mesangial-immune-deposits-but-not-with-progression-of-iga-nephropathy
#6
Perrine Jullien, Blandine Laurent, Guillaume Claisse, Ingrid Masson, Miriana Dinic, Damien Thibaudin, Francois Berthoux, Eric Alamartine, Christophe Mariat, Nicolas Maillard
Activation of complement through the alternative pathway has a key role in the pathogenesis of IgA nephropathy (IgAN). Large, international, genome-wide association studies have shown that deletion of complement factor H-related genes 1 and 3 (CFHR3,1Δ) is associated with a reduced risk of developing IgAN, although the prognostic value of these deletions in IgAN remains unknown. Here, we compared the renal outcomes of patients with IgAN according to their CFHR3,1Δ genotype. This retrospective, monocentric cohort study included 639 white patients with biopsy-proven IgAN since 1979 (mean age at diagnosis, 40...
November 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29107384/binding-of-human-complement-c1-sterase-inhibitor-to-leptospira-spp
#7
Leandro Carvalho Dantas Breda, Silvio Arruda Vasconcellos, Dewton de Moraes Vasconcelos, Lourdes Isaac
Leptospirosis is an important zoonosis of global importance caused by bacteria Leptospira spp. Pathogenic Leptospira is resistant to Complement System killing while non-pathogenic Leptospira is rapidly killed by exposure to normal human serum (NHS). Pathogenic Leptospira interact with Complement Regulators such as Factor H, C4b binding protein and Vitronectin avoiding Complement activation and killing by Alternative and Classical Pathways. One important regulator is C1-inhibitor (C1INH) that interacts with C1s or MASPs controlling the cleavage of C4 and C2 molecules, thereby inhibiting the activation of the Classical and Lectin Pathways...
October 13, 2017: Immunobiology
https://www.readbyqxmd.com/read/29095988/changes-in-extracellular-matrix-cause-rpe-cells-to-make-basal-deposits-and-activate-the-alternative-complement-pathway
#8
Rosario Fernandez-Godino, Kinga M Bujakowska, Eric A Pierce
The design of efficient therapies for age-related macular degeneration (AMD) is limited by our understanding of the pathogenesis of basal deposits, which form between retinal pigment epithelium (RPE) and Bruch's membrane (BrM) early in disease, and involve activation of the complement system. To investigate the roles of BrM, RPE and complement in AMD, we generated abnormal extracellular matrix (ECM) using CRISPR-edited ARPE-19 cells. We introduced to these cells the p.R345W mutation in EFEMP1, which causes early-onset macular degeneration...
October 31, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29093712/factor-h-related-fhr-1-and-fhr-2-form-homo-and-heterodimers-while-fhr-5-circulates-only-as-homodimer-in-human-plasma
#9
Anna E van Beek, Richard B Pouw, Mieke C Brouwer, Gerard van Mierlo, Judy Geissler, Pleuni Ooijevaar-de Heer, Martin de Boer, Karin van Leeuwen, Theo Rispens, Diana Wouters, Taco W Kuijpers
The complement factor H-related (FHR) proteins are hypothesized to fine-tune the regulatory role of complement factor H (FH) in the alternative pathway of the complement system. Moreover, FHR-1, FHR-2, and FHR-5 have been proposed to be dimers, which further complicates accurate analysis. As FHRs are highly similar among themselves and toward FH, obtaining specific reagents for quantification of serum levels and functional analysis is challenging. In this study, we generated antibodies and developed ELISAs to measure FHR-1, FHR-2, and FHR-5 in serum...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29078325/necroptosis-controls-net-generation-and-mediates-complement-activation-endothelial-damage-and-autoimmune-vasculitis
#10
Adrian Schreiber, Anthony Rousselle, Jan Ulrich Becker, Anne von Mässenhausen, Andreas Linkermann, Ralph Kettritz
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes life-threatening autoimmune diseases affecting every organ, including the kidneys, where they cause necrotizing crescentic glomerulonephritis. ANCA activates neutrophils and activated neutrophils damage the endothelium, leading to vascular inflammation and necrosis. Better understanding of neutrophil-mediated AAV disease mechanisms may reveal novel treatment strategies. Here we report that ANCA induces neutrophil extracellular traps (NETs) via receptor-interacting protein kinase (RIPK) 1/3- and mixed-lineage kinase domain-like (MLKL)-dependent necroptosis...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29061764/the-structural-basis-for-complement-inhibition-by-gigastasin-a-protease-inhibitor-from-the-giant-amazon-leech
#11
Siew Siew Pang, Lakshmi C Wijeyewickrema, Lilian Hor, Sheareen Tan, Emilie Lameignere, Edward M Conway, Anna M Blom, Frida C Mohlin, Xuyu Liu, Richard J Payne, James C Whisstock, Robert N Pike
Complement is crucial to the immune response, but dysregulation of the system causes inflammatory disease. Complement is activated by three pathways: classical, lectin, and alternative. The classical and lectin pathways are initiated by the C1r/C1s (classical) and MASP-1/MASP-2 (lectin) proteases. Given the role of complement in disease, there is a requirement for inhibitors to control the initiating proteases. In this article, we show that a novel inhibitor, gigastasin, from the giant Amazon leech, potently inhibits C1s and MASP-2, whereas it is also a good inhibitor of MASP-1...
October 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29061482/irc2-bf-a-yeast-and-borrelia-responsive-component-of-the-complement-system-from-the-hard-tick-ixodes-ricinus
#12
Veronika Urbanová, Ondřej Hajdušek, Radek Šíma, Zdeněk Franta, Helena Hönig-Mondeková, Lenka Grunclová, Pavla Bartošová-Sojková, Marie Jalovecká, Petr Kopáček
Ticks possess components of a primordial complement system that presumably play a role in the interaction of the tick immune system with tick-borne pathogens and affect their transmission. Here we characterized a novel complement component, tagged as IrC2/Bf, from the hard tick Ixodes ricinus, the principal vector of Lyme disease in Europe. IrC2/Bf is a multi-domain molecule composed of 5-7 CCP modules, varied by alternative splicing, followed by a von Willebrand factor A domain and a C-terminal trypsin-like domain...
October 20, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29054837/altered-metabolic-landscape-in-idh-mutant-gliomas%C3%A2-affects-phospholipid-energy-and-oxidative-stress-pathways
#13
Fred Fack, Saverio Tardito, Guillaume Hochart, Anais Oudin, Liang Zheng, Sabrina Fritah, Anna Golebiewska, Petr V Nazarov, Amandine Bernard, Ann-Christin Hau, Olivier Keunen, William Leenders, Morten Lund-Johansen, Jonathan Stauber, Eyal Gottlieb, Rolf Bjerkvig, Simone P Niclou
Heterozygous mutations in NADP-dependent isocitrate dehydrogenases (IDH) define the large majority of diffuse gliomas and are associated with hypermethylation of DNA and chromatin. The metabolic dysregulations imposed by these mutations, whether dependent or not on the oncometabolite D-2-hydroxyglutarate (D2HG), are less well understood. Here, we applied mass spectrometry imaging on intracranial patient-derived xenografts of IDH-mutant versus IDH wild-type glioma to profile the distribution of metabolites at high anatomical resolution in situ This approach was complemented by in vivo tracing of labeled nutrients followed by liquid chromatography-mass spectrometry (LC-MS) analysis...
October 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29050988/physiological-and-immune-response-of-juvenile-rainbow-trout-to-dietary-bovine-lactoferrin
#14
Trinh Dinh Khuyen, Syaghalirwa N M Mandiki, Valérie Cornet, Jessica Douxfils, Stéphane Betoulle, Peter Bossier, Felipe E Reyes-López, Lluis Tort, Patrick Kestemont
Lactoferrin, a large multifunctional glycoprotein, is involved in many physiological functions but its immunomodulatory pathways are not well characterized in fish. The objective of the present study was to investigate the temporal effect of dietary bovine lactoferrin (BLf) at low (0.1%) and high (1%) on immunological organs of rainbow trout juveniles. BLf diets did not affect specific growth rate, haematocrit, splenic index, spleen respiratory burst activity as well as humoral (mIgM) and neutrophils (MPO) gene expressions after short term - 35 days (D35) and long term nutrient test - 51 days (D51) of feeding...
October 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29040213/importance-of-the-complement-alternative-pathway-in-serum-chemotactic-activity-during-sepsis
#15
Ganqiong Xu, Yan Feng, Dan Li, Qichang Zhou, Wei Chao, Lin Zou
Serum chemotactic activity is important in regulating neutrophil migration. The ability of neutrophils to migrate to infectious site is crucial for host effective pathogen control, but unregulated neutrophil activation can also cause tissue damage. During bacterial sepsis, the complement alternative pathway (AP) is massively activated in blood and tissues and reportedly contributes to sepsis pathogenesis. Complement factor B (FB) is an essential component of the AP activation. However, the impact of FB/AP activation on blood chemotactic activity during bacterial infection is unclear...
October 16, 2017: Shock
https://www.readbyqxmd.com/read/29031100/discovery-of-a-new-mechanism-for-regulation-of-plant-triacylglycerol-metabolism-the-peanut-diacylglycerol-acyltransferase-1-gene-family-transcriptome-is-highly-enriched-in-alternative-splicing-variants
#16
Ling Zheng, Jay Shockey, Feng Guo, Lingmin Shi, Xinguo Li, Lei Shan, Shubo Wan, Zhenying Peng
Triacylglycerols (TAGs) are the most important energy storage form in oilseed crops. Diacylglycerol acyltransferase (DGAT) catalyzes the rate-limiting step of the Kennedy pathway of TAG biosynthesis. To date, little is known about the regulation of DGAT activity in peanut (Arachis hypogaea), an agronomically important oilseed crop that is cultivated in many parts of the world. In this study, seven distinct forms of type 1 DGAT (AhDGAT1.1-AhDGAT1.7) were identified, cloned, and characterized. Comparisons of the nucleotide sequences and gene structures revealed many different splicing variants of AhDGAT1, some of which displayed different organ-specific expression patterns...
October 6, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/29030465/cluster-analysis-identifies-distinct-pathogenetic-patterns-in-c3-glomerulopathies-immune-complex-mediated-membranoproliferative-gn
#17
Paraskevas Iatropoulos, Erica Daina, Manuela Curreri, Rossella Piras, Elisabetta Valoti, Caterina Mele, Elena Bresin, Sara Gamba, Marta Alberti, Matteo Breno, Annalisa Perna, Serena Bettoni, Ettore Sabadini, Luisa Murer, Marina Vivarelli, Marina Noris, Giuseppe Remuzzi
Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN...
October 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29021784/synthetic-peptides-to-target-stringent-response-controlled-virulence-in-a-pseudomonas-aeruginosa-murine-cutaneous-infection-model
#18
Daniel Pletzer, Heidi Wolfmeier, Manjeet Bains, Robert E W Hancock
Microorganisms continuously monitor their surroundings and adaptively respond to environmental cues. One way to cope with various stress-related situations is through the activation of the stringent stress response pathway. In Pseudomonas aeruginosa this pathway is controlled and coordinated by the activity of the RelA and SpoT enzymes that metabolize the small nucleotide secondary messenger molecule (p)ppGpp. Intracellular ppGpp concentrations are crucial in mediating adaptive responses and virulence. Targeting this cellular stress response has recently been the focus of an alternative approach to fight antibiotic resistant bacteria...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29021347/multiple-pathways-facilitate-the-biogenesis-of-mammalian-tail-anchored-proteins
#19
Joseph Casson, Michael McKenna, Sarah Haßdenteufel, Naama Aviram, Richard Zimmerman, Stephen High
Tail-anchored (TA) proteins are transmembrane proteins with a single C-terminal transmembrane domain, which functions as both their subcellular targeting signal and membrane anchor. We show that a TRC40 knockout in cultured human cells has a relatively minor effect on model endogenous TA proteins, despite their apparent reliance on this pathway in vitro These findings support recent evidence that the canonical TRC40 pathway is not essential for TA protein biogenesis in vivo We therefore investigated the possibility that other ER targeting routes can complement the TRC40 pathway and identified roles for both the SRP pathway and the recently described mammalian SND pathway in TA protein biogenesis...
October 11, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29018449/mechanisms-cofactors-and-augmenting-factors-involved-in-anaphylaxis
#20
REVIEW
Rosa Muñoz-Cano, Mariona Pascal, Giovanna Araujo, M J Goikoetxea, Antonio L Valero, Cesar Picado, Joan Bartra
Anaphylaxis is an acute and life-threatening systemic reaction. Many triggers have been described, including food, drug, and hymenoptera allergens, which are the most frequently involved. The mechanisms described in anaphylactic reactions are complex and implicate a diversity of pathways. Some of these mechanisms may be key to the development of the anaphylactic reaction, while others may only modify its severity. Although specific IgE, mast cells, and basophils are considered the principal players in anaphylaxis, alternative mechanisms have been proposed in non-IgE anaphylactic reactions...
2017: Frontiers in Immunology
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