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https://www.readbyqxmd.com/read/28237029/c5ar-contributes-to-the-weak-th1-profile-induced-by-an-outbreak-strain-of-mycobacterium-tuberculosis
#1
Carmen Alejandra Sabio Y García, Noemí Yokobori, Juan Ignacio Basile, Luciana Balboa, Alejandra González, Beatriz López, Viviana Ritacco, Silvia de la Barrera, María Del Carmen Sasiain
C5a anaphylatoxin is a component of the complement system involved in the modulation of T-cell polarization. Herein we investigated whether C5a receptors, C5aR and C5L2, modulate the cytokine profiles induced by Mycobacterium tuberculosis (Mtb). We analyzed the impact of both receptors on T helper cell polarization induced by the multidrug resistant outbreak strain named M, which is a poor IFN-γ inducer compared with the laboratory strain H37Rv. To this aim, we first blocked C5aR or C5L2 of peripheral blood monocytes (Mo) from patients with tuberculosis and healthy donors, then we stimulated the Mo either with H37Rv or the M strain, and finally we analyzed cytokine profiles of Mo/macrophages (MΦ) and CD4(+) T-cells...
March 2017: Tuberculosis
https://www.readbyqxmd.com/read/28231307/differential-regulation-of-c5a-receptor-1-in-innate-immune-cells-during-the-allergic-asthma-effector-phase
#2
Fanny Ender, Anna V Wiese, Inken Schmudde, Jing Sun, Tillman Vollbrandt, Peter König, Yves Laumonnier, Jörg Köhl
C5a drives airway constriction and inflammation during the effector phase of allergic asthma, mainly through the activation of C5a receptor 1 (C5aR1). Yet, C5aR1 expression on myeloid and lymphoid cells during the allergic effector phase is ill-defined. Recently, we generated and characterized a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse. Here, we used this reporter strain to monitor C5aR1 expression in airway, pulmonary and lymph node cells during the effector phase of OVA-driven allergic asthma...
2017: PloS One
https://www.readbyqxmd.com/read/28228558/the-ribosomal-protein-s19-suppresses-antitumor-immune-responses-via-the-complement-c5a-receptor-1
#3
Maciej M Markiewski, Surya Kumari Vadrevu, Sharad K Sharma, Navin Kumar Chintala, Shanawaz Ghouse, Jun-Hung Cho, David P Fairlie, Yvonne Paterson, Aristotelis Astrinidis, Magdalena Karbowniczek
Relatively little is known about factors that initiate immunosuppression in tumors and act at the interface between tumor cells and host cells. In this article, we report novel immunosuppressive properties of the ribosomal protein S19 (RPS19), which is upregulated in human breast and ovarian cancer cells and released from apoptotic tumor cells, whereupon it interacts with the complement C5a receptor 1 expressed on tumor infiltrating myeloid-derived suppressor cells. This interaction promotes tumor growth by facilitating recruitment of these cells to tumors...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28225753/complement-drives-glucosylceramide-accumulation-and-tissue-inflammation-in-gaucher-disease
#4
Manoj K Pandey, Thomas A Burrow, Reena Rani, Lisa J Martin, David Witte, Kenneth D Setchell, Mary A Mckay, Albert F Magnusen, Wujuan Zhang, Benjamin Liou, Jörg Köhl, Gregory A Grabowski
Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28190533/the-roles-of-a-ribosomal-protein-s19-polymer-in-a-mouse-model-of-carrageenan-induced-acute-pleurisy
#5
Koji Yamanegi, Toru Kawakami, Naoko Yamada, Shunsuke Kumanishi, Hiroyuki Futani, Keiji Nakasho, Hiroshi Nishiura
C5-deficient mice usually present moderate neutrophil activation during the initiation phase of acute inflammation. Conversely, C5a receptor (C5aR)-deficient mice show unusually excessive activation of neutrophils. We identified the ribosomal protein S19 (RP S19) polymer, which is cross-linked at Lys122 and Gln137 by transglutaminases in apoptotic neutrophils, as a second C5aR ligand during the resolution phase of acute inflammation. The RP S19 polymer promotes apoptosis via the neutrophil C5aR and phagocytosis via the macrophage C5aR...
February 7, 2017: Immunobiology
https://www.readbyqxmd.com/read/28173736/the-alternative-receptor-for-complement-component-5a-c5ar2-conveys-neuroprotection-in-traumatic-spinal-cord-injury
#6
Patrick Biggins, Faith Brennan, Stephen Taylor, Trent Woodruff, Marc Ruitenberg
This study investigated the role of the secondary receptor for complement activation fragment C5a, C5aR2, in secondary inflammatory pathology following contusive spinal cord injury (SCI) in mice. <i>C5ar2<sup>-/-</sup></i> mice exhibited decreased intraparenchymal TNFα and IL-6 acutely after injury but these reductions did not translate into improved outcomes. We show that loss of C5aR2 leads to increased lesion volumes, reduced myelin sparing and significantly worsened recovery from SCI in <i>C5ar2<sup>-/-</sup></i> animals compared to wild-type (WT) controls...
February 7, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28167912/c5a-regulates-il-1%C3%AE-production-and-leukocyte-recruitment-in-a-murine-model-of-monosodium-urate-crystal-induced-peritonitis
#7
Hanif J Khameneh, Adrian W S Ho, Federica Laudisi, Heidi Derks, Matheswaran Kandasamy, Baalasubramanian Sivasankar, Gim Gee Teng, Alessandra Mortellaro
Gouty arthritis results from the generation of monosodium urate (MSU) crystals within joints. These MSU crystals elicit acute inflammation characterized by massive infiltration of neutrophils and monocytes that are mobilized by the pro-inflammatory cytokine IL-1β. MSU crystals also activate the complement system, which regulates the inflammatory response; however, it is unclear whether or how MSU-mediated complement activation is linked to IL-1β release in vivo, and the various roles that might be played by individual components of the complement cascade...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28143910/paper-of-note-in-science-immunology-2-7
#8
John F Foley
This month's article shows how the complement C5a receptor initiates the recruitment of neutrophils into joint endothelium in a mouse model of arthritis.
January 31, 2017: Science Signaling
https://www.readbyqxmd.com/read/28139294/c5-inhibition-prevents-renal-failure-in-a-mouse-model-of-lethal-c3-glomerulopathy
#9
Allison Lesher Williams, Damodar Gullipalli, Yoshiyasu Ueda, Sayaka Sato, Lin Zhou, Takashi Miwa, Kenneth S Tung, Wen-Chao Song
C3 glomerulopathy is a potentially life-threatening disease of the kidney caused by dysregulated alternative pathway complement activation. The specific complement mediator(s) responsible for kidney injury in C3 glomerulopathy are yet to be defined and no specific therapy is currently available. We previously developed a mouse model of lethal C3 glomerulopathy with factor H and properdin gene double mutations. Therefore, we used this model to examine the role of C5 and C5a receptor (C5aR) in the pathogenesis of the disease...
January 27, 2017: Kidney International
https://www.readbyqxmd.com/read/28128456/pharmacological-inhibition-of-complement-c5a-c5ar1-signalling-ameliorates-disease-pathology-in-the-hsod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#10
John D Lee, Vinod Kumar, Jenny Nt 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 upregulated in ALS, with recent studies indicating that the activation product C5a may accelerate disease progression via its receptor, C5aR1. We therefore aimed to examine the therapeutic effect of C5aR1 antagonism in hSOD1(G93A) mice, the most widely used preclinical model of ALS. EXPERIMENTAL APPROACH: The selective and orally active C5aR1 antagonist, PMX205, was administered to hSOD1(G93A) mice via their drinking water, both pre- and post-disease onset...
January 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28117704/above-and-beyond-c5a-receptor-targeting-by-staphylococcal-leucotoxins-retrograde-transport-of-panton-valentine-leucocidin-and-%C3%AE-hemolysin
#11
Gaëlle Zimmermann-Meisse, Gilles Prévost, Emmanuel Jover
Various membrane receptors associated with the innate immune response have recently been identified as mediators of the cellular action of Staphylococcus aureus leucotoxins. Two of these, the Panton-Valentine leucotoxin LukS-PV/LukF-PV and the γ-hemolysin HlgC/HlgB, bind the C5a complement-derived peptide receptor. These leucotoxins utilize the receptor to induce intracellular Ca(2+) release from internal stores, other than those activated by C5a. The two leucotoxins are internalized with the phosphorylated receptor, but it is unknown whether they divert retrograde transport of the receptor or follow another pathway...
January 20, 2017: Toxins
https://www.readbyqxmd.com/read/28107529/complement-activation-and-stat4-expression-are-associated-with-early-inflammation-in-diabetic-wounds
#12
Kenji M Cunnion, Neel K Krishna, Haree K Pallera, Angela Pineros-Fernandez, Magdielis Gregory Rivera, Pamela S Hair, Brittany P Lassiter, Ryan Huyck, Mary A Clements, Antoinette F Hood, George T Rodeheaver, Patrick S Cottler, Jerry L Nadler, Anca D Dobrian
: Diabetic non-healing wounds are a major clinical problem. The mechanisms leading to poor wound healing in diabetes are multifactorial but unresolved inflammation may be a major contributing factor. The complement system (CS) is the most potent inflammatory cascade in humans and contributes to poor wound healing in animal models. Signal transducer and activator of transcription 4 (STAT4) is a transcription factor expressed in immune and adipose cells and contributes to upregulation of some inflammatory chemokines and cytokines...
2017: PloS One
https://www.readbyqxmd.com/read/28096298/mfg-e8-derived-peptide-attenuates-adhesion-and-migration-of-immune-cells-to-endothelial-cells
#13
Yohei Hirano, Weng-Lang Yang, Monowar Aziz, Fangming Zhang, Barbara Sherry, Ping Wang
Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) plays an immunomodulatory role in inflammatory diseases. MFG-E8-derived short peptide (MSP68) greatly reduces neutrophil infiltration and injury in the lung during sepsis. In this study, we examined the effect of MSP68 on chemotaxis of various immune cells and its regulatory mechanism. Bone marrow-derived neutrophils (BMDNs) from C57BL/6 mice, human monocyte THP-1 cell line, and human T lymphocyte Jurkat cell line were used for adhesion and migration assays using a Transwell method in the presence of MSP68...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28078911/c5a-increases-the-injury-to-primary-neurons-elicited-by-fibrillar-amyloid-beta
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
January 31, 2017: Oncotarget
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