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https://www.readbyqxmd.com/read/28078911/c5a-increases-the-injury-to-primary-neurons-elicited-by-fibrillar-amyloid-beta
#1
Michael X Hernandez, Pouya Namiranian, Eric Nguyen, Maria I Fonseca, Andrea J Tenner
C5aR1, the proinflammatory receptor for C5a, is expressed in the central nervous system on microglia, endothelial cells, and neurons. Previous work demonstrated that the C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in two Alzheimer's Disease (AD) mouse models. However, the cellular mechanisms of this protection have not been definitively demonstrated. Here, primary cultured mouse neurons treated with exogenous C5a show reproducible loss of MAP-2 staining in a dose-dependent manner within 24 hr of treatment, indicative of injury to neurons...
February 2017: ASN Neuro
https://www.readbyqxmd.com/read/28078079/looking-forward-to-new-targeted-treatments-for-chronic-spontaneous-urticaria
#2
REVIEW
Emek Kocatürk, Marcus Maurer, Martin Metz, Clive Grattan
The introduction of omalizumab to the management of chronic spontaneous urticaria (CSU) has markedly improved the therapeutic possibilities for both, patients and physicians dealing with this disabling disease. But there is still a hard core of patients who do not tolerate or benefit from existing therapies and who require effective treatment. Novel approaches include the use of currently available drugs off-licence, investigational drugs currently undergoing clinical trials and exploring the potential for therapies directed at pathophysiological targets in CSU...
2017: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/28067347/fc-microparticles-can-modulate-the-physical-extent-and-magnitude-of-complement-activity
#3
Brandon Alexander Holt, Michael C Bellavia, Daniel Potter, David White, Sean R Stowell, Todd Sulchek
The complement system is an integral component of the humoral immune system, and describes a cascade of interacting proteins responsible for the opsonization and lysis of foreign pathogens, in addition to the recruitment of immune cells. However, complement activation is also implicated in the progression and complication of immune dysfunctions such as sepsis. Microparticle (MP) biomaterials capable of tuning the local magnitude of serum complement activation could improve complement-mediated cytotoxicity to serum-resistant bacteria or calm an overactive immune response during sepsis...
January 9, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28058672/neuroprotective-effects-of-intravenous-immunoglobulin-are-mediated-through-inhibition-of-complement-activation-and-apoptosis-in-a-rat-model-of-sepsis
#4
Figen Esen, Gunseli Orhun, Perihan Ergin Ozcan, Evren Senturk, Melike Kucukerden, Murat Giris, Ugur Akcan, Canan Ugur Yilmaz, Nurcan Orhan, Nadir Arican, Mehmet Kaya, Sema Bilgic Gazioglu, Erdem Tuzun
BACKGROUND: Intravenous (IV) immunoglobulin (Ig) treatment is known to alleviate behavioral deficits and increase survival in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. METHODS: Sepsis was induced by cecal ligation perforation (CLP) in rats. The animals were divided into five groups: sham, control, CLP + saline, CLP + immunoglobulin G (IgG) (250 mg/kg, iv), and CLP + immunoglobulins enriched with immunoglobulin M (IgGAM) (250 mg/kg, iv)...
December 2017: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/28053974/the-role-of-complement-activation-in-copd-exacerbation-recovery
#5
John-Paul Westwood, Alexander J Mackay, Gavin Donaldson, Samuel J Machin, Jadwiga A Wedzicha, Marie Scully
Rise in sputum complement (C3a, C5a) levels during COPD exacerbation is associated with recovery time http://ow.ly/ZaPj303xxPf.
October 2016: ERJ Open Research
https://www.readbyqxmd.com/read/28052346/properdin-deficiency-protects-from-5-fluorouracil-induced-small-intestinal-mucositis-in-a-complement-activation-independent-il-10-dependent-mechanism
#6
Umang Jain, Craig A Midgen, Trent M Woodruff, Wilhelm J Schwaeble, Cordula M Stover, Andrew W Stadnyk
Intestinal mucositis is a serious complication of chemotherapy that leads to significant morbidity that may require dose or drug adjustments. Specific mitigating strategies for mucositis are unavailable, partly due to an incomplete understanding of the pathogenic mechanisms. We have previously shown an effect of properdin, a positive regulator of complement activation, in models of colitis. Here we use properdin deficient (P(KO) ) mice to interrogate the role of properdin and complement in small intestinal mucositis...
January 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28052000/association-of-c5l2-genetic-polymorphisms-with-coronary-artery-disease-in-a-han-population-in-xinjiang-china
#7
Ying-Ying Zheng, Xiang Xie, Yi-Tong Ma, Zhen-Yan Fu, Xiang Ma, Yi-Ning Yang, Xiao-Mei Li, Shuo Pan, Dilare Adi, Bang-Dang Chen, Fen Liu
BACKGROUND: C5aR-like receptor 2 (C5L2) has been identified as a receptor for the inflammatory factor Complement 5a (C5a) and acylation-stimulating protein (ASP). ASP binding to C5L2 leading to a net accumulation of TG stores and glucose transporter. The aim of the present study is to evaluate the association of the SNPs of C5L2 gene with coronary artery disease (CAD) in a Chinese population. METHODS: We examined the role of the tagging single nucleotide polymorphisms (SNPs) of C5L2 gene for CAD using a case-control design...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035470/the-clinical-and-laboratory-features-of-chinese-han-anti-factor-h-autoantibody-associated-hemolytic-uremic-syndrome
#8
Di Song, Xiao-Rong Liu, Zhi Chen, Hui-Jie Xiao, Jie Ding, Shu-Zhen Sun, Hong-Yan Liu, Wei-Yi Guo, Su-Xia Wang, Feng Yu, Ming-Hui Zhao
BACKGROUND: Anti-complement factor H (CFH) autoantibody-associated hemolytic uremic syndrome (HUS) is a severe sub-type of HUS. METHODS: We assessed the clinical and renal pathological features, circulating complement levels, and genetic background of Chinese pediatric patients with this sub-type of HUS. Thirty-three consecutive patients with acute kidney injury who tested positive for serum anti-CFH autoantibodies were enrolled in this study. RESULTS: All of the eight patients who underwent renal biopsies presented with changes typical of thrombotic microangiopathy, especially changes in chronic characteristics...
December 29, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28033684/cellular-reactions-and-compensatory-tissue-re-organization-during-spontaneous-recovery-after-spinal-cord-injury-in-neonatal-mice
#9
Rishab S Chawla, Mark Züchner, Maria Mastrangelopoulou, François M Lambert, Joel C Glover, Jean-Luc Boulland
Following incomplete spinal cord injuries, neonatal mammals display a remarkable degree of behavioral recovery. Previously, we have demonstrated in neonatal mice a wholesale re-establishment and reorganization of synaptic connections from some descending axon tracts (Boulland et al., 2013). To assess the potential cellular mechanisms contributing to this recovery, we have here characterized a variety of cellular sequelae following thoracic compression injuries, focusing particularly on cell loss and proliferation, inflammation and reactive gliosis, and the dynamics of specific types of synaptic terminals...
December 29, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/28033061/c5l2-receptor-represses-brain-derived-neurotrophic-factor-secretion-in-lipoteichoic-acid-stimulated-pulp-fibroblasts
#10
F Chmilewsky, I About, S H Chung
The anaphylatoxin C5a constitutes a powerful fragment generated by complement system activation. Interestingly, this complement active fragment is also an important mediator of tissue regeneration. Recent findings suggest that C5a could be an initial signal orchestrating pulp nerve sprouting beneath carious injury, a critical step in dentin-pulp regeneration. Indeed, the expression and activation of the C5a active receptor (C5aR/CD88) by injured pulp fibroblasts controls the direction of neurite outgrowth toward carious injuries by modulating the secretion of brain-derived neurotrophic factor (BDNF) by pulp fibroblasts...
January 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28028363/c5a-c5ar-pathway-is-essential-for-up-regulating-sphk1-expression-through-p38-mapk-activation-in-acute-liver-failure
#11
Yan-Chang Lei, Chun-Lei Lu, Ling Chen, Ke Ge, Ling-Ling Yang, Wen Li, Yuan-Hua Wu
AIM: To investigate the role of the complement 5a (C5a)/C5a receptor (C5aR) pathway in the pathogenesis of acute liver failure (ALF) in a mouse model. METHODS: BALB/c mice were randomly assigned to different groups, and intraperitoneal injections of lipopolysaccharide (LPS)/D-galactosamine (D-GalN) (600 mg/kg and 10 μg/kg) were used to induce ALF. The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase (ALT) levels, at different time points within a 1-wk period, were detected with a biochemistry analyzer...
December 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28019718/excretions-secretions-from-medicinal-larvae-lucilia-sericata-inhibit-complement-activation-by-two-mechanisms
#12
Tetsuro Tamura, Gwendolyn Cazander, Suzan H M Rooijakkers, Leendert A Trouw, Peter H Nibbering
Larvae of the blowfly Lucilia sericata facilitate wound healing by removing dead tissue and biofilms from non-healing and necrotic wounds. Another beneficial action of larvae and their excretions/secretions (ES) is down-regulation of excessive inflammation. As prolonged complement activation is key to excessive inflammation, the aim of this study was to elucidate the mechanisms underlying the anti-complement activities of ES. Results revealed that heat sensitive serine proteases in ES degrade multiple complement proteins in all steps of the three complement activation pathways...
December 26, 2016: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28002390/therapeutic-hypothermia-modulates-complement-factor-c3a-and-c5a-levels-in-a-rat-model-of-hypoxic-ischemic-encephalopathy
#13
Tushar A Shah, Jasmine E Nejad, Haree K Pallera, Frank A Lattanzio, Rawad Farhat, Parvathi S Kumar, Pamela S Hair, W Thomas Bass, Neel K Krishna
BACKGROUND: Therapeutic hypothermia (HT) is the only intervention that improves outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). However, the multifactorial mechanisms by which HT impacts HIE are incompletely understood. The complement system plays a major role in the pathogenesis of ischemia-reperfusion injuries such as HIE. We have previously demonstrated that HT modulates complement activity in vitro. METHODS: Term equivalent rat pups were subjected to unilateral carotid ligation followed by hypoxia (8% O2) for 45 minutes to simulate HIE...
December 21, 2016: Pediatric Research
https://www.readbyqxmd.com/read/28000366/hemocompatiblilty-evaluation-of-poly-1-8-octanediol-citrate-blend-polyethersulfone-membranes
#14
Muhamad Zulhilmi Zailani, Ahmad Fauzi Ismail, Siti Hamimah Sheikh Abdul Kadir, Mohd Hafiz Dzarfan Othman, Pei Sean Goh, Hasrinah Hasbullah, Mohd Sohaimi Abdullah, Be Cheer Ng, Fatmawati Kamal
In this study, poly (1,8- octanediol citrate) (POC) was used to modify polyethersufone (PES) based membrane to enhance its hemocompatibility. Different compositions of POC (0-3%) were added into the polyethersulfone (PES) dope solutions and polyvinylpyrrolidone (PVP) was used as pore forming agent. The hemocompatible POC modified PES membranes were fabricated through phase-inversion technique. The prepared membranes were characterized using attenuated total reflectance-fourier transform infrared (ATR-FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Atomic-force microscopy (AFM), contact angle, Zeta-potential, membrane porosity and pore size and pure water flux (PWF) and BSA rejection...
December 21, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27979430/classical-complement-pathway-activation-in-the-nasal-tissue-of-patients-with-chronic-rhinosinusitis
#15
Griet A Van Roey, Christopher C Vanison, Jeffanie Wu, Julia H Huang, Lydia A Suh, Roderick G Carter, James E Norton, Stephanie Shintani-Smith, David B Conley, Kevin C Welch, Anju T Peters, Leslie C Grammer, Kathleen E Harris, Kathryn E Hulse, Atsushi Kato, Whitney W Stevens, Robert C Kern, Robert P Schleimer, Bruce K Tan
BACKGROUND: Complement plays a major role in inflammatory diseases but its involvement and mechanisms of activation in chronic rhinosinusitis (CRS) are not known. OBJECTIVES: Following earlier studies discovering autoantibodies in CRS, we sought to investigate the nature, extent, and location of complement activation in nasal tissue of patients with CRS. Specifically, we were interested in whether antibody-mediated activation via the classical pathway was a major mechanism for complement activation in CRS...
December 12, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27974594/complement-mediated-inhibition-of-adiponectin-regulates-perivascular-inflammation-and-vascular-injury-in-hypertension
#16
Cheng-Chao Ruan, Yu Ma, Qian Ge, Yan Li, Li-Min Zhu, Ying Zhang, Ling-Ran Kong, Qi-Hong Wu, Fanghong Li, Lixian Cheng, Allan Z Zhao, Ding-Liang Zhu, Ping-Jin Gao
Perivascular adipose tissue (PVAT)-derived adiponectin (APN) is a secreted adipokine that protects against hypertension-related cardiovascular injury. However, the regulation of APN expression in hypertension remains to be explored. In this study, we demonstrated that down-regulation of APN was associated with complement activation in the PVAT of desoxycorticosterone acetate (DOCA)-salt hypertensive mice. Complement 3-deficient hypertensive mice were protected from ANP decrease in the PVAT. APN deficiency blockaded the protective effects of complement inhibition against hypertensive vascular injury...
December 14, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27933491/nlrp3-is-required-for-complement-mediated-caspase-1-and-il-1beta-activation-in-ich-short-title-for-running-head-nlrp3-is-required-for-ich
#17
Sheng-Tao Yao, Fang Cao, Jia-Lin Chen, Wei Chen, Rui-Ming Fan, Gang Li, You-Chao Zeng, Song Jiao, Xiang-Ping Xia, Chong Han, Qi-Shan Ran
Complement-mediated inflammation plays a vital role in intracerebral hemorrhage (ICH), implicating pro-inflammatory factor interleukin-1beta (IL-1β) secretion. Brain samples and contralateral hemiencephalon were all collected and detected by Western blot. NLRP3 expression was located by dual immunofluorescence staining at 1, 3, and 5 days post-ICH. Brain water content was examined post-ICH. The neural deficit scores were evaluated by observers blindly. ILs were detected by ELISA. SiRNAs targeting NLRP3 (siNLRP3), siASC, and siControl were injected to inhibit NLRP3 function...
December 8, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27932254/investigating-possible-biological-targets-of-bj-crp-the-first-cysteine-rich-secretory-protein-crisp-isolated-from-bothrops-jararaca-snake-venom
#18
Marina E Lodovicho, Tássia R Costa, Carolina P Bernardes, Danilo L Menaldo, Karina F Zoccal, Sante E Carone, José C Rosa, Manuela B Pucca, Felipe A Cerni, Eliane C Arantes, Jan Tytgat, Lúcia H Faccioli, Luciana S Pereira-Crott, Suely V Sampaio
Cysteine-rich secretory proteins (CRISPs) are commonly described as part of the protein content of snake venoms, nevertheless, so far, little is known about their biological targets and functions. Our study describes the isolation and characterization of Bj-CRP, the first CRISP isolated from Bothrops jararaca snake venom, also aiming at the identification of possible targets for its actions. Bj-CRP was purified using three chromatographic steps (Sephacryl S-200, Source 15Q and C18) and showed to be an acidic protein of 24...
January 4, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27931779/complement-and-sepsis-induced-heart-dysfunction
#19
Fatemeh Fattahi, Peter A Ward
It is well known that cardiac dysfunction develops during sepsis in both humans and in rodents (rats, mice). These defects appear to be reversible, since after "recovery" from sepsis, cardiac dysfunction disappears and the heart returns to its function that was present before the onset of sepsis. Our studies, using in vivo and in vitro models, have demonstrated that C5a and its receptors (C5aR1 and C5aR2) play key roles in cardiac dysfunction developing during sepsis. Use of a neutralizing antibody to C5a largely attenuates cardiac dysfunction and other adverse events developing during sepsis...
December 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27916272/regulation-and-function-of-anaphylatoxins-and-their-receptors-in-allergic-asthma
#20
Yves Laumonnier, Anna V Wiese, Julia Figge, Christian Karsten
Allergic asthma is a disease of the airways driven by maladaptive T helper 2 (Th2) and Th17 immune response against harmless, airborne substances. The hallmarks of this disease are airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation and mucus overproduction. Distinct dendric cell (DC) subsets together with airway epithelial and pulmonary vascular endothelial cells play critical roles in allergen sensing and in driving T cell differentiation towards Th2 and Th17 effector or regulatory T cells (Treg)...
December 1, 2016: Molecular Immunology
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