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Complement pathway

Nicolás De Silva, Mirian Samblas, J Alfredo Martínez, Fermín I Milagro
Obesity is usually associated with low-grade inflammation, which determines the appearance of comorbidities like atherosclerosis and insulin resistance. Infiltrated macrophages in adipose tissue are partly responsible of this inflammatory condition. Numerous studies point to the existence of close intercommunication between macrophages and adipocytes and pay particular attention to the proinflammatory cytokines released by both cell types. However, it has been recently described that in both, circulation and tissue level, there are extracellular vesicles (including microvesicles and exosomes) containing miRNAs, mRNAs, and proteins that can influence the inflammatory response...
March 20, 2018: Journal of Physiology and Biochemistry
Marzia Dolcino, Andrea Pelosi, Piera Filomena Fiore, Giuseppe Patuzzo, Elisa Tinazzi, Claudio Lunardi, Antonio Puccetti
Systemic sclerosis (SSc) is a rare connective tissue disease characterized by three pathogenetic hallmarks: vasculopathy, dysregulation of the immune system, and fibrosis. A particular feature of SSc is the increased frequency of some types of malignancies, namely breast, lung, and hematological malignancies. Moreover, SSc may also be a paraneoplastic disease, again indicating a strong link between cancer and scleroderma. The reason of this association is still unknown; therefore, we aimed at investigating whether particular genetic or epigenetic factors may play a role in promoting cancer development in patients with SSc and whether some features are shared by the two conditions...
2018: Frontiers in Immunology
Peng Cui, Hongxia Niu, Wanliang Shi, Shuo Zhang, Wenhong Zhang, Ying Zhang
Persister cells are metabolically quiescent multi-drug tolerant fraction of a genetically sensitive bacterial population and are thought to be responsible for relapse of many persistent infections. Persisters can be formed naturally in the stationary phase culture, and also can be induced by bacteriostatic antibiotics. However, the molecular basis of bacteriostatic antibiotic induced persister formation is unknown. Here, we established a bacteriostatic antibiotic induced persister model and screened the Escherichia coli single gene deletion mutant library for mutants with defect in rifampin or tetracycline induced persistence to ofloxacin...
2018: Frontiers in Microbiology
Steven A Harris, Elizabeth A Harris
This review focuses on research in the areas of epidemiology, neuropathology, molecular biology and genetics that implicates herpes simplex virus type 1 (HSV-1) as a causative agent in the pathogenesis of sporadic Alzheimer's disease (AD). Molecular mechanisms whereby HSV-1 induces AD-related pathophysiology and pathology, including neuronal production and accumulation of amyloid beta (Aβ), hyperphosphorylation of tau proteins, dysregulation of calcium homeostasis, and impaired autophagy, are discussed. HSV-1 causes additional AD pathologies through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis...
2018: Frontiers in Aging Neuroscience
Xiangzhi Meng, Thomas Kaever, Bo Yan, Paula Traktman, Dirk M Zajonc, Bjoern Peters, Shane Crotty, Yan Xiang
Vaccinia virus (VACV) A14 is a major envelope protein and a dominant antibody target in the smallpox vaccine. However, the role of anti-A14 antibodies in immunity against orthopoxviruses is unclear. Here, we characterized 22 A14 monoclonal antibodies (mAb) from two mice immunized with VACV. Epitope mapping showed that 21 mAbs targeted the C-terminal hydrophilic region, while one mAb recognized the middle region predicted to be across the viral envelope from the C-terminus. However, none of the mAbs bound to virions in studies with electron microscopy...
March 17, 2018: Virology
Ulkem Kocoglu Barlas, Hasan Serdar Kıhtır, Nilufer Goknar, Melike Ersoy, Nihal Akcay, Esra Sevketoglu
BACKGROUND: Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Atypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant mortality and high risk of progression to end-stage kidney disease. It is mostly caused by dysregulation of the alternative complement pathway. Cobalamin C (Cbl C) defect is a genetic disorder of cobalamin metabolism and is a rare cause of HUS. CASE-DIAGNOSIS/TREATMENT: We present a 6-month-old male infant who was admitted to the pediatric intensive care unit (PICU) due to restlessness, severe hypertension, anemia, respiratory distress, and acute kidney injury...
March 20, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Takuma Wada, Takeshi Fukuda, Masahiro Shimomura, Yuta Inoue, Masaru Kawanishi, Reiko Tasaka, Tomoyo Yasui, Kazuo Ikeda, Toshiyuki Sumi
The standard treatment for locally advanced uterine cervical cancer is concurrent chemoradiotherapy. Successful neoadjuvant chemotherapy (NAC) may reduce tumor size and facilitate a hysterectomy, thereby improving the prognosis for patients with locally advanced cervical cancer. In contrast, unsuccessful NAC may worsen the prognosis because if a hysterectomy is not possible, the change in treatment plan may delay the initiation of core treatment. Therefore, there is a need to identify biomarkers that predict the efficacy of NAC in patients with uterine cervical cancer...
March 2018: Oncology Letters
Sarah E Sartain, Nancy A Turner, Joel L Moake
Atypical hemolytic uremic syndrome (aHUS) and bone marrow transplantation-associated thrombotic microangiopathy (TA-TMA) are associated with excessive activation of the alternative complement pathway (AP) and with severe renal - and rarely, cerebral - microvascular damage. Here, we compared AP activation and regulation in human glomerular and brain microvascular endothelial cells (GMVECs and BMVECs, respectively) unstimulated or stimulated by the proinflammatory cytokine, tumor necrosis factor (TNF). Compared with GMVECs and under both experimental conditions, BMVECs had increased gene expression of the AP-related genes C3 , CFB , and C5 , and decreased expression of CFD This was associated with increased expression in BMVECs (relative to GMVECs) of the genes for surface and soluble regulatory molecules ( CD46 , THBD , CD55 , CFI , and CFH ) suppressing formation of the AP C3 and C5 convertases...
March 19, 2018: Journal of Biological Chemistry
Franziska Just, Michael Oster, Kirsten Büsing, Luisa Borgelt, Eduard Murani, Siriluck Ponsuksili, Petra Wolf, Klaus Wimmers
BACKGROUND: In monogastric animals, phosphorus (P) homeostasis is maintained by regulating intestinal absorption, bone mobilization, and renal excretion. Since P is a non-renewable resource, a shortage is imminent due to widespread over-usage in the farming and animal husbandry industries. As a consequence, P efficiency should be improved in pig production. We sought to characterize the transcriptional response in re-/absorbing and excreting tissues in pigs to diets varying in calcium: phosphorus ratios...
March 20, 2018: BMC Genomics
Yered Pita-Juarez, Gabriel Altschuler, Sokratis Kariotis, Wenbin Wei, Katjusa Koler, Claire Green, Rudolph Tanzi, Winston Hide
A goal of genomics is to understand the relationships between biological processes. Pathways contribute to functional interplay within biological processes through complex but poorly understood interactions. However, limited functional references for global pathway relationships exist. Pathways from databases such as KEGG and Reactome provide discrete annotations of biological processes. Their relationships are currently either inferred from gene set enrichment within specific experiments, or by simple overlap, linking pathway annotations that have genes in common...
March 19, 2018: PLoS Computational Biology
Anirban Banerjee, Christopher C Silliman, Ernest E Moore, Monika Dzieciatskowa, Marguerite Kelher, Angela Sauaia, Kenneth Jones, Michael P Chapman, Eduardo Gonzalez, Hunter B Moore, Angelo D'Alessandro, Erik Peltz, Benjamin E Huebner, Peter Einerson, James Chandler, Arsen Ghasabayan, Kirk Hansen
BACKGROUND: Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology. METHODS: Blood samples were collected in the field or at Emergency Department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions...
March 16, 2018: Journal of Trauma and Acute Care Surgery
Stephanie Portillo-Ledesma, Lía M Randall, Derek Parsonage, Joaquín Dalla Rizza, P Andrew Karplus, Leslie B Poole, Ana Denicola, Gerardo Ferrer-Sueta
Two-cysteine peroxiredoxins (Prx) have a three-step catalytic cycle consisting of (1) reduction of peroxide and formation of sulfenic acid on the enzyme, (2) condensation of the sulfenic acid with a thiol to form disulfide, also known as resolution, and (3) reduction of the disulfide by a reductant protein. By following changes in protein fluorescence, we have studied the pH dependence of reaction 2 in human peroxiredoxins 1, 2 and 5, and in Salmonella typhimurium AhpC and obtained rate constants for the reaction and p Ka values of the thiol and sulfenic acid involved for each system...
March 19, 2018: Biochemistry
Chloé I Charendoff, Lisa Bouchier-Hayes
The caspase family of proteases play essential roles in apoptosis and innate immunity. Among these, a subgroup known as initiator caspases are the first to be activated in these pathways. This group includes caspase-2, -8, and -9, as well as the inflammatory caspases, caspase-1, -4, and -5. The initiator caspases are all activated by dimerization following recruitment to specific multiprotein complexes called activation platforms. Caspase Bimolecular Fluorescence Complementation (BiFC) is an imaging-based approach where split fluorescent proteins fused to initiator caspases are used to visualize the recruitment of initiator caspases to their activation platforms and the resulting induced proximity...
March 5, 2018: Journal of Visualized Experiments: JoVE
Chunmei Piao, Wen-Mei Zhang, Tao-Tao Li, Cong-Cong Zhang, Shulan Qiu, Yan Liu, Sa Liu, Ming Jin, Li-Xin Jia, Wen-Chao Song, Jie Du
Inflammatory cells such as macrophages can play a pro-tumorigenic role in the tumor stroma. Tumor-associated macrophages (TAMs) generally display an M2 phenotype with tumor-promoting activity; however, the mechanisms regulating the TAM phenotype remain unclear. Complement 5a (C5a) is a cytokine-like polypeptide that is generated during complement system activation and is known to promote tumor growth. Herein, we investigated the role of C5a on macrophage polarization in colon cancer metastasis in mice. We found that deficiency of the C5a receptor (C5aR) severely impairs the metastatic ability of implanted colon cancer cells...
March 15, 2018: Experimental Cell Research
Baptiste Couvy-Duchesne, Victoria O'Callaghan, Richard Parker, Natalie Mills, Katherine M Kirk, Jan Scott, Anna Vinkhuyzen, Daniel F Hermens, Penelope A Lind, Tracey A Davenport, Jane M Burns, Melissa Connell, Brendan P Zietsch, James Scott, Margaret J Wright, Sarah E Medland, John McGrath, Nicholas G Martin, Ian B Hickie, Nathan A Gillespie
PURPOSE: The Nineteen and Up study (19Up) assessed a range of mental health and behavioural problems and associated risk factors in a genetically informative Australian cohort of young adult twins and their non-twin siblings. As such, 19Up enables detailed investigation of genetic and environmental pathways to mental illness and substance misuse within the Brisbane Longitudinal Twin Sample (BLTS). PARTICIPANTS: Twins and their non-twin siblings from Queensland, Australia; mostly from European ancestry...
March 17, 2018: BMJ Open
Gaetan Barbet, Leif E Sander, Matthew Geswell, Irina Leonardi, Andrea Cerutti, Iliyan Iliev, J Magarian Blander
Live vaccines historically afford superior protection, yet the cellular and molecular mechanisms mediating protective immunity remain unclear. Here we found that vaccination of mice with live, but not dead, Gram-negative bacteria heightened follicular T helper cell (Tfh) differentiation, germinal center formation, and protective antibody production through the signaling adaptor TRIF. Complementing the dead vaccine with an innate signature of bacterial viability, bacterial RNA, recapitulated these responses...
March 9, 2018: Immunity
Quan Zhou, Li Hong, Jing Wang
PURPOSE: The aim of this study was to elucidate the molecular mechanisms and to identify the key genes and pathways for pelvic organ prolapse (POP) using bioinformatics analysis. METHODS: The microarray data for GSE53868 included 12 POP and 12 non-POP anterior vaginal wall samples. Differentially expressed genes (DEGs) were identified by GEO2R online tool. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database, and a DEG-associated protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape...
March 15, 2018: Archives of Gynecology and Obstetrics
Hui Fang, Yang Zhang, Ning Li, Gang Wang, Zhi Liu
Bullous pemphigoid (BP) is an autoimmune and inflammatory skin disease associated with subepidermal blistering and autoantibodies directed against the hemidesmosomal components BP180 and BP230. Animal models of BP were developed by passively transferring anti-BP180 IgG into mice, which recapitulates the key features of human BP. By using these in vivo model systems, key cellular and molecular events leading to the BP disease phenotype are identified, including binding of pathogenic IgG to its target, complement activation of the classical pathway, mast cell degranulation, and infiltration and activation of neutrophils...
2018: Frontiers in Immunology
Anas H Abu-Humaidan, Malin Elvén, Andreas Sonesson, Peter Garred, Ole E Sørensen
The complement system is an ancient part of the innate immune system important for both tissue homeostasis and host defense. However, bacteria like Staphylococcus aureus (SA) possess elaborative mechanisms for evading both the complement system and other parts of the immune system. One of these evasive mechanisms-important in causing chronic and therapy resistant infections-is the intracellular persistence in non-immune cells. The objective of our study was to investigate whether persistent intracellular SA infection of epidermal keratinocytes resulted in complement activation...
2018: Frontiers in Immunology
Shuang-An Li, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Juan Yang, Xu Tang, He-Qun Shi, Xiao-Qiu Zhou
In this study, we investigated the effects of dietary myo-inositol on the intestinal immune barrier function and related signaling pathway in young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (221.33 ± 0.84 g) were fed six diets containing graded levels of myo-inositol (27.0, 137.9, 286.8, 438.6, 587.7 and 737.3 mg/kg) for 10 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila. The results indicated that compared with the optimal dietary myo-inositol level, myo-inositol deficiency (27...
March 12, 2018: Fish & Shellfish Immunology
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