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Complement receptor 3

Amanda Mener, Seema R Patel, Connie M Arthur, Satheesh Chonat, Andreas Wieland, Manjula Santhanakrishnan, Jingchun Liu, Cheryl L Maier, Ryan P Jajosky, Kathryn Girard-Pierce, Ashley Bennett, Patricia E Zerra, Nicole H Smith, Jeanne E Hendrickson, Sean R Stowell
RBC alloimmunization represents a significant immunological challenge for patients requiring lifelong transfusion support. The majority of clinically relevant non-ABO(H) blood group antigens have been thought to drive antibody formation through T cell-dependent immune pathways. Thus, we initially sought to define the role of CD4+ T cells in formation of alloantibodies to KEL, one of the leading causes of hemolytic transfusion reactions. Unexpectedly, our findings demonstrated that KEL RBCs actually possess the ability to induce antibody formation independent of CD4+ T cells or complement component 3 (C3), two common regulators of antibody formation...
November 15, 2018: JCI Insight
Nirmal K Banda, Dhruv Desai, Robert I Scheinman, Rasmus Pihl, Hideharu Sekine, Teizo Fujita, Vibha Sharma, Annette G Hansen, Peter Garred, Steffen Thiel, Anna Borodovsky, V Michael Holers
Mannan-binding lectin-associated serine protease 3 (MASP-3) regulates the alternative pathway of complement and is predominantly synthesized in the liver. The role of liver-derived MASP-3 in the pathogenesis of rheumatoid arthritis (RA) is unknown. We hypothesized that liver-derived MASP-3 is essential for the development of joint damage and that targeted inhibition of MASP-3 in the liver can attenuate arthritis. We used MASP-3-specific small interfering RNAs (siRNAs) conjugated to N-acetylgalactosamine (GalNAc) to specifically target the liver via asialoglycoprotein receptors...
September 2018: ImmunoHorizons
Shari Bodofsky, Katarina Liberatore, Lauren Pioppo, Dominic Lapadula, Lily Thompson, Susanna Birnbaum, George McClung, Akshara Kartik, Sheila Clever, Bruce Wightman
The nhr-67 nuclear receptor gene of Caenorhabditis elegans encodes the ortholog of the Drosophila tailless and vertebrate Tlx genes. In C. elegans, nhr-67 plays multiple roles in the development of the uterus during L2 and L3 larval stages. Four pre-VU cells are born in the L2 stage and form the precursor complement for the ventral surface of the mature uterus. One of the four pre-VU cells becomes the anchor cell (AC), which exits the cell cycle and differentiates, while the remaining three VU cells serve as stem cells that populate the ventral uterus...
November 4, 2018: Gene Expression Patterns: GEP
Xinyi Zhou, Peng Zhang, Qian Wang, Sisi Xia, Ning Ji, Yi Ding, Qi Wang
Type 2 diabetic mellitus is manifested by metabolic impairments with high prevalence worldwide, of which periodontitis represents a typical oral complication (also called diabetic periodontitis). Oral epithelia bear the brunt of periodontal damage from microscopic intruders; thus the defense function of epithelial cells is of vital significance. We have previously proved that 25-hydroxyvitamin D3 (25-OHD3 ) altered the expression of cathelicidin antimicrobial peptide in oral epithelial cells in vitro. Herein, we discovered that 25-OHD3 intraperitoneal injection attenuated periodontal inflammation by promoting cathelicidin production in gingival epithelia and reducing fasting glucose of diabetic mice...
2018: Journal of Nutritional Science and Vitaminology
Marion Steger, Marta Bermejo-Jambrina, Teodor Yordanov, Johannes Wagener, Axel A Brakhage, Verena Pittl, Lukas A Huber, Hubertus Haas, Cornelia Lass-Flörl, Wilfried Posch, Doris Wilflingseder
Complement system and dendritic cells (DCs) form - beside neutrophils and macrophages - the first line of defense to combat fungal infections. Therefore, we here studied interactions of these first immune elements with Aspergillus fumigatus lacking ß-1,3-glucans (fks1tetOn rep under repressed conditions) to mechanistically explain the mode of action of echinocandins in more detail. Echinocandins are cell wall active agents blocking β-glucan synthase, making the A. fumigatus fks1tetOn mutant a good model to study immune-modulatory actions of these drugs...
October 29, 2018: Virulence
Naomi Benne, Janine van Duijn, Fernando Lozano Vigario, Romain J T Leboux, Peter van Veelen, Johan Kuiper, Wim Jiskoot, Bram Slütter
Atherosclerosis is the predominant underlying pathology of many types of cardiovascular disease and is one of the leading causes of death worldwide. It is characterized by the retention of oxidized low-density lipoprotein (ox-LDL) in lipid-rich macrophages (foam cells) in the intima of arteries. Autoantigens derived from oxLDL can be used to vaccinate against atherosclerosis. However, a major challenge is the induction of antigen-specific Tregs in a safe and effective way. Here we report that liposomes containing the anionic phospholipid 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) induce Tregs that are specific for the liposomes' cargo...
October 23, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
C R Mehta, L Liu, C Theuer
Background: Major challenges in clinical trials of ultra orphan oncology diseases include limited patient availability and paucity of reliable prior data for estimating the treatment effect and, therefore, determining optimal sample size. Angiosarcoma (AS), a particularly aggressive form of soft tissue sarcoma with an incidence of about 2,000 cases per year in the United States and Europe is poorly addressed by current systemic therapies. Pazopanib, an inhibitor of vascular endothelial growth factor receptor (VEGFR) is approved for the treatment of AS, with modest benefit...
October 24, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
José M Porcel
The use of biomarkers on pleural fluid (PF) specimens may assist the decision-making process and enhance clinical diagnostic pathways. Three paradigmatic examples are heart failure, tuberculosis and, particularly, malignancy. An elevated PF concentration of the amino-terminal fragment of probrain natriuretic peptide (>1500 pg/ml) is a hallmark of acute decompensated heart failure. Adenosine deaminase, interferon-γ and interleukin-27 are three valuable biomarkers for diagnosing tuberculous pleurisy, yet only the first has been firmly established in clinical practice...
January 2018: Therapeutic Advances in Respiratory Disease
Shubin Li, Yihang Yin, Hong Yu
Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer; however, the specific genes and signaling pathways involved in this cancer remain largely unclear. The present study analyzed three profile datasets, GSE6004, GSE29265 and GSE60542, which were comprised of 47 PTC and 41 normal thyroid tissue samples, to identify key genes and pathways associated with PTC. Initially, differentially-expressed genes (DEGs) between PTC and normal thyroid tissue were screened using R 3.4.0 (2017-04-21, R Foundation, Vienna, Austria, http://www...
November 2018: Oncology Letters
Júlia Canet-Pons, Ralf Schubert, Ruth Pia Duecker, Roland Schrewe, Sandra Wölke, Matthias Kieslich, Martina Schnölzer, Andreas Chiocchetti, Georg Auburger, Stefan Zielen, Uwe Warnken
Autosomal recessive ataxia telangiectasia (A-T) is characterized by radiosensitivity, immunodeficiency, and cerebellar neurodegeneration. A-T is caused by inactivating mutations in the ataxia telangiectasiamutated (ATM) gene, a serine-threonine protein kinase involved in DNA damage response and excitatory neurotransmission. The selective vulnerability of cerebellar Purkinje neurons (PN) to A-T is not well understood. Employing global proteomic profiling of cerebrospinal fluid from patients at ages around 15 years, we detected reduced calbindin, reelin, cerebellin-1, cerebellin-3, protocadherin fat 2, sempahorin 7A, and increased apolipoprotein B and J peptides...
October 21, 2018: Neurogenetics
Jaroslava Dekkerová, Jose L Lopez-Ribot, Helena Bujdáková
Fungal biofilm has remained a serious medical problem that complicates treatment of mycoses. In particular, once biofilms are formed, they display high levels of resistance against most common antifungals. Candida auris is currently considered as a serious emerging fungal pathogen frequently exhibiting high levels of resistance to antifungals. Recent studies have confirmed that C. auris shares similarity with Candida albicans in regards to virulence-associated proteins involved in adherence and biofilm development...
October 16, 2018: European Journal of Clinical Microbiology & Infectious Diseases
Hui Xu, Lu Zhang, Birgitta Heyman
Specific IgG antibodies, passively administered together with erythrocytes, suppress antibody responses against the erythrocytes. Although used to prevent alloimmunization in Rhesus (Rh)D-negative women carrying RhD-positive fetuses, the mechanism behind is not understood. In mice, IgG suppresses efficiently in the absence of Fcγ-receptors and complement, suggesting an Fc-independent mechanism. In line with this, suppression is frequently restricted to the epitopes to which IgG binds. However, suppression of responses against epitopes not recognized by IgG has also been observed thus arguing against Fc-independence...
October 16, 2018: Scientific Reports
Gail A Bishop, Laura L Stunz, Bruce S Hostager
The adaptor protein TNF receptor-associated factor 3 (TRAF3) serves as a powerful negative regulator in multiple aspects of B cell biology. Early in vitro studies in transformed cell lines suggested the potential of TRAF3 to inhibit signaling by its first identified binding receptor, CD40. However, because the canonical TRAF3 binding site on many receptors also mediates binding of other TRAFs, and whole-mouse TRAF3 deficiency is neonatally lethal, an accurate understanding of TRAF3's specific functions was delayed until conditional TRAF3-deficient mice were produced...
2018: Frontiers in Immunology
Zaher A Radi
Pathophysiologically, the classification of acute kidney injury (AKI) can be divided into three categories: (1) prerenal, (2) intrinsic, and (3) postrenal. Emerging evidence supports the involvement of renal tubular epithelial cells and the innate and adaptive arms of the immune system in the pathogenesis of intrinsic AKI. Pro-inflammatory damage-associated molecular patterns, pathogen-associated molecular patterns, hypoxia inducible factors, toll-like receptors, complement system, oxidative stress, adhesion molecules, cell death, resident renal dendritic cells, neutrophils, T and B lymphocytes, macrophages, natural killer T cells, cytokines, and secreted chemokines contribute to the immunopathogenesis of AKI...
October 3, 2018: Toxicologic Pathology
Quan Wang, Yilin Shen, Bin Ye, Haixia Hu, Cui Fan, Tan Wang, Yuqin Zheng, Jingrong Lv, Yan Ma, Mingliang Xiang
To identify differences in gene expression profiles of infected cells between thyroid carcinoma (C), thyroid adenoma (A) and normal thyroid (N) epithelial cells, differentially expressed genes were identified using three pairwise comparisons with the GEO2R online tool. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to classify them at the functional level. The most significant cluster in the N vs. A pairwise comparison had four hub genes: Insulin-like growth factor 2, Von Willebrand factor (VWF), multimerin 1 (MMRN1) and complement factor D (CFD)...
September 20, 2018: Oncology Reports
Fanxing Meng, Yuanyuan Zhang, Jianbo Zhou, Ming Li, Ge Shi, Rixin Wang
Unlike the normal anadromous lifestyle, Chinese native Dolly Varden char (Salvelinus malma) is locked in land and lives in fresh water lifetime. To explore the effect of freshwater adaption on its immune system, we constructed a pooled cDNA library of hepatopancreas and spleen of Chinese freshwater Dolly Varden char (S. malma). A total of 27,829 unigenes were generated from 31,233 high-quality transcripts and 17,670 complete open reading frames (ORF) were identified. Totally 25,809 unigenes were successfully annotated and it classified more native than adaptive immunity-associated genes, and more genes involved in toll-like receptor signal pathway than those in complement and coagulation cascades (51 vs 3), implying the relative more important role of toll-like receptors than the complement system under bacterial injection for the freshwater Dolly Varden char...
September 25, 2018: Fish & Shellfish Immunology
Hilde L Orrem, Per H Nilsson, Søren E Pischke, Ola Kleveland, Arne Yndestad, Karin Ekholt, Jan K Damås, Terje Espevik, Bjørn Bendz, Bente Halvorsen, Ida Gregersen, Rune Wiseth, Geir Ø Andersen, Thor Ueland, Lars Gullestad, Pål Aukrust, Andreas Barratt-Due, Tom E Mollnes
Background: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the anaphylatoxin receptors in whole blood from non-ST-elevation myocardial infarction (NSTEMI) patients. Separately, anaphylatoxin receptor expression in peripheral blood mononuclear cells (PBMC) from patients with different entities of CAD was investigated...
2018: Frontiers in Immunology
Daphnée Brulé, Clizia Villano, Laura J Davies, Lucie Trdá, Justine Claverie, Marie-Claire Héloir, Annick Chiltz, Marielle Adrian, Benoît Darblade, Pablo Tornero, Lena Stransfeld, Freddy Boutrot, Cyril Zipfel, Ian B Dry, Benoit Poinssot
Chitin, a major component of fungal cell walls, is a well-known pathogen-associated molecular pattern (PAMP) that triggers defense responses in several mammal and plant species. Here we show that two chitooligosaccharides, chitin and chitosan, act as PAMPs in grapevine (Vitis vinifera) as they elicit immune signaling events, defense gene expression, and resistance against fungal diseases. To identify their cognate receptors, the grapevine family of LysM receptor kinases (LysM-RKs) was annotated and their gene expression profiles characterized...
September 26, 2018: Plant Biotechnology Journal
Andres F Vallejo, Robert C Read, Myriam Arevalo-Herrera, Sócrates Herrera, Tim Elliott, Marta E Polak
OBJECTIVES: To dissect the transcriptional networks underpinning immune cells responses during primary Plasmodium vivax infection of healthy human adults. METHODS: We conducted network co-expression analysis of next-generation RNA sequencing data from whole blood from P. vivax and P. falciparum controlled human malaria infection (CHMI) of healthy naïve and malaria-exposed volunteers. Single cell transcription signatures were used to deconvolute the bulk RNA-Seq data into cell-specific signals...
November 2018: Journal of Infection
Yuxing Zhao, Cheng Luo, Jinliang Chen, Yue Sun, Die Pu, Ankang Lv, Shiyu Zhu, Jing Wu, Meili Wang, Jing Zhou, Zhiyin Liao, Kexiang Zhao, Qian Xiao
Diabetes is considered as a risk for cognitive decline, which is characterized by neurodegenerative alteration and innate immunity activation. Recently, complement 3 (C3), the critical central component of complement system, has been reported to play a key role in neurodegenerative alterations under pathological condition. Receptor for advanced glycation end products (RAGE) activation is confirmed to mediate several inflammatory cytokines production. However, whether C3 activation participates in the diabetic neuropathology and whether this process is regulated by RAGE activation remains unknown...
December 2018: Journal of Cellular and Molecular Medicine
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