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https://www.readbyqxmd.com/read/29912438/an-oncolytic-measles-virus-sensitive-group-3-medulloblastoma-model-in-immune-competent-mice
#1
Sangeet Lal, Diego Carrera, Joanna J Phillips, William A Weiss, Corey Raffel
Background: Oncolytic measles virus (MV) is effective in xenograft models of many tumor types in immune-compromised mice. However, no murine cell line exists that is tumorigenic, grows in immune-competent mice, and is killed by MV. The lack of such a model prevents an examination of the effect of the immune system on MV oncotherapy. Methods: Cerebellar stem cells from human CD46-transgenic immunocompetent mice were transduced to express Sendai virus C-protein, murine C-Myc, and Gfi1b proteins...
June 14, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29909495/the-neuro-immune-regulators-niregs-promote-tissue-resilience-a-vital-component-of-the-host-s-defense-strategy-against-neuroinflammation
#2
REVIEW
Yosra Bedoui, Jim W Neal, Philippe Gasque
An effective protective inflammatory response in the brain is crucial for the clearance of pathogens (e.g. microbes, amyloid fibrils, prionSC ) and should be closely regulated. However, the CNS seems to have limited tissue resilience to withstand the detrimental effects of uncontrolled inflammation compromising functional recovery and tissue repair. Newly described neuro-immune-regulators (NIREGs) are functionally related proteins regulating the severity and duration of the host inflammatory response. NIREGs such as CD200, CD47 and CX3CL1 are vital for increasing tissue resilience and are constitutively expressed by neurons...
June 16, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29902483/cd46-is-a-potent-co-stimulatory-receptor-for-expansion-of-human-ifn-%C3%AE-producing-cd8-t-cells
#3
Aida S Hansen, Josefine Slater, Mette Biltoft, Bettina B Bundgaard, Bjarne K Møller, Per Höllsberg
Similar to CD4+ T cells, precursor CD8+ T cells are thought to depend on a co-stimulatory signal through CD28 for proliferation and differentiation into effector cells. CD46 is another co-stimulatory receptor that promotes differentiation of CD4+ T-helper cells type 1 (Th1 cells) into a regulatory phenotype with a switch from IFN-γ towards IL-10-secretion over time. Whether CD46 exerts a similar function on CD8+ T cells remains to be fully elucidated. Here, we demonstrate that CD46 co-stimulation induced secretion of IFN-γ as well as expansion of IFN-γ-secreting CD8+ T cells...
June 11, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29898782/expression-of-human-cd46-and-trans-complementation-by-murine-adenovirus-1-fails-to-allow-productive-infection-by-a-group-b-oncolytic-adenovirus-in-murine-cancer-cells
#4
Janet Lei, Egon J Jacobus, William K Taverner, Kerry D Fisher, Silvio Hemmi, Katy West, Lorna Slater, Fred Lilley, Alice Brown, Brian Champion, Margaret R Duffy, Len W Seymour
BACKGROUND: Oncolytic viruses are currently experiencing accelerated development in several laboratories worldwide, with some forty-seven clinical trials currently recruiting. Many oncolytic viruses combine targeted cytotoxicity to cancer cells with a proinflammatory cell lysis. Due to their additional potential to express immunomodulatory transgenes, they are also often known as oncolytic viral vaccines. However, several types of oncolytic viruses are human-specific and the lack of suitable immune-competent animal models complicates biologically relevant evaluation of their vaccine potential...
June 13, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29867953/association-between-promoter-polymorphisms-in-cd46-and-cd59-in-kidney-donors-and-transplant-outcome
#5
Laura A Michielsen, Arjan D van Zuilen, Tineke Kardol-Hoefnagel, Marianne C Verhaar, Henny G Otten
Complement regulating proteins, including CD46, CD55, and CD59, protect cells against self-damage. Because of their expression on the donor endothelium, they are hypothesized to be involved in accommodation. Polymorphisms in their promoter regions may affect their expression. The aim of this study was to investigate if donor polymorphisms in complement regulating proteins influence kidney transplant outcomes. We included 306 kidney transplantations between 2005 and 2010. Five polymorphisms in the promoters of CD46, CD55, and CD59 were genotyped...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29789357/reactivation-of-%C3%AE-globin-in-adult-%C3%AE-yac-mice-after-ex-vivo-and-in-vivo-hematopoietic-stem-cell-genome-editing
#6
Chang Li, Nikoletta Psatha, Pavel Sova, Sucheol Gil, Hongjie Wang, Jiho Kim, Chandana Kulkarni, Cristina Valensisi, R David Hawkins, George Stamatoyannopoulos, André Lieber
Disorders involving β-globin gene mutations, mainly β-thalassemia and sickle cell disease, represent a major target for hematopoietic stem/progenitor cell (HSPC) gene therapy. This includes CRISPR/Cas9-mediated genome editing approaches in adult CD34+ cells aimed toward the re-activation of fetal γ-globin expression in red blood cells. Because models involving erythroid differentiation of CD34+ cells have limitations in assessing γ-globin re-activation, we focused on human β-globin locus transgenic (β-YAC) mice...
May 22, 2018: Blood
https://www.readbyqxmd.com/read/29766024/integrating-hdad5-35-vectors-as-a-new-platform-for-hsc-gene-therapy-of-hemoglobinopathies
#7
Chang Li, Nikoletta Psatha, Hongjie Wang, Manvendra Singh, Himanshu Bhusan Samal, Wenli Zhang, Anja Ehrhardt, Zsuzsanna Izsvák, Thalia Papayannopoulou, André Lieber
We generated an integrating, CD46-targeted, helper-dependent adenovirus HDAd5/35++ vector system for hematopoietic stem cell (HSC) gene therapy. The ∼12-kb transgene cassette included a β-globin locus control region (LCR)/promoter driven human γ-globin gene and an elongation factor alpha-1 (EF1α)-mgmtP140K expression cassette, which allows for drug-controlled increase of γ-globin-expressing erythrocytes. We transduced bone marrow lineage-depleted cells from human CD46-transgenic mice and transplanted them into lethally irradiated recipients...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29751531/computational-analysis-of-the-interaction-energies-between-amino-acid-residues-of-the-measles-virus-hemagglutinin-and-its-receptors
#8
Fengqi Xu, Shigenori Tanaka, Hirofumi Watanabe, Yasuhiro Shimane, Misako Iwasawa, Kazue Ohishi, Tadashi Maruyama
Measles virus (MV) causes an acute and highly devastating contagious disease in humans. Employing the crystal structures of three human receptors, signaling lymphocyte-activation molecule (SLAM), CD46, and Nectin-4, in complex with the measles virus hemagglutinin (MVH), we elucidated computationally the details of binding energies between the amino acid residues of MVH and those of the receptors with an ab initio fragment molecular orbital (FMO) method. The calculated inter-fragment interaction energies (IFIEs) revealed a number of significantly interacting amino acid residues of MVH that played essential roles in binding to the receptors...
May 3, 2018: Viruses
https://www.readbyqxmd.com/read/29732228/de-novo-atypical-haemolytic-uremic-syndrome-after-kidney-transplantation
#9
Arnaud Devresse, Martine de Meyer, Selda Aydin, Karin Dahan, Nada Kanaan
De novo thrombotic microangiopathy (TMA) can occur after kidney transplantation. An abnormality of the alternative pathway of complement must be suspected and searched for, even in presence of a secondary cause. We report the case of a 23-year-old female patient who was transplanted with a kidney from her mother for end-stage renal disease secondary to Hinman syndrome. Early after transplantation, she presented with 2 episodes of severe pyelonephritis, associated with acute kidney dysfunction and biological and histological features of TMA...
2018: Case Reports in Nephrology
https://www.readbyqxmd.com/read/29731087/seven-years-of-experiences-of-preclinical-experiments-of-xeno-heart-transplantation-of-pig-to-non-human-primate-cynomolgus-monkey
#10
S J Lee, J S Kim, H K Chee, I J Yun, K S Park, H S Yang, J H Park
BACKGROUND: The absolute shortage of donors compared with patients requiring transplantation is currently an unsolved problem, and the only possible solution may be xenotransplantation. To establish a successful clinical trial, a preclinical study using nonhuman primates is essential. Starting in November 2011, our team initiated heterotopic abdominal heart xenotransplantation, the first in the Republic of Korea. We present here the initial 7-year results. METHODS: A total of 22 xenotransplantation procedures have been performed since 2011...
May 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29716854/a-study-of-the-interaction-between-h-pylori-mice-passage-strains-and-gastric-epithelial-cells
#11
Inayatur Rahman, Muhammad Idrees, Mohammad Waqas, Abdul Karim
Helicobacter pylori (H. pylori) infections are very serious health problem that are further worsened by increasing/developing resistance to the current antibiotics. Therefore, new therapeutic agents are needed for H. pylori eradication. Use of a CD46 derived peptide (P3) as bactericidal agent against H. pylori has shown high activity rate in vivo and this study examines the changes in H. pylori features in response to effect of P3 treatment.AGS cells were infected with H. pylori wild type strain 67:21 and its mice passage strains (P3 treated and untreated strains) and further examined using immunoblotting assay, FACS and Urease activity analysis...
May 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29693588/relative-contribution-of-cellular-complement-inhibitors-cd59-cd46-and-cd55-to-parainfluenza-virus-5-inhibition-of-complement-mediated-neutralization
#12
Yujia Li, Griffith D Parks
The complement system is a part of the innate immune system that viruses need to face during infections. Many viruses incorporate cellular regulators of complement activation (RCA) to block complement pathways and our prior work has shown that Parainfluenza virus 5 (PIV5) incorporates CD55 and CD46 to delay complement-mediated neutralization. In this paper, we tested the role of a third individual RCA inhibitor CD59 in PIV5 interactions with complement pathways. Using a cell line engineered to express CD59, we show that small levels of functional CD59 are associated with progeny PIV5, which is capable of blocking assembly of the C5b-C9 membrane attack complex (MAC)...
April 25, 2018: Viruses
https://www.readbyqxmd.com/read/29662661/targeting-oncogenic-ras-by-the-clostridium-perfringens-toxin-tpel
#13
Björn Schorch, Hannah Heni, Nour-Imene Zahaf, Tilman Brummer, Marina Mione, Gudula Schmidt, Panagiotis Papatheodorou, Klaus Aktories
Clostridium perfringens toxin TpeL belongs to the family of large clostridial glycosylating toxins. The toxin causes N-acetylglucosaminylation of Ras proteins at threonine35 thereby inactivating the small GTPases. Here, we show that all main types of oncogenic Ras proteins (H-Ras, K-Ras and N-Ras) are modified by the toxin in vitro and in vivo . Toxin-catalyzed modification of Ras was accompanied by inhibition of the MAP kinase pathway. Importantly, TpeL inhibited the paradoxical activation of the MAP kinase pathway induced by the BRAF inhibitor Vemurafenib in the human melanoma cell line SBCL2...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29644059/mutations-in-membrane-cofactor-protein-cd46-gene-in-indian-children-with-hemolytic-uremic-syndrome
#14
Priyanka Khandelwal, Shweta Birla, Divya Bhatia, Mamta Puraswani, Himanshi Saini, Aditi Sinha, Pankaj Hari, Arundhati Sharma, Arvind Bagga
Background: Mutations in the CD46 gene account for an important proportion of patients with atypical hemolytic uremic syndrome (aHUS) who characteristically show multiple relapses, no response to plasma exchange and low recurrence risk in allograft. We screened for mutations in CD46 in patients with and without circulating anti-factor H (FH) antibodies-associated aHUS. Methods: We estimated CD46 surface expression by flow cytometry and sequenced the CD46 gene in 23 and 56 patients with and without circulating anti-FH antibodies, respectively...
April 2018: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29566171/genetic-analysis-of-the-complement-pathway-in-c3-glomerulopathy
#15
Weiwei Zhao, Yin Ding, Jianping Lu, Tao Zhang, Dacheng Chen, Haitao Zhang, Caihong Zeng, Zhihong Liu, Huimei Chen
Background: C3 glomerulopathy often presents with a membranoproliferative glomerulonephritis (MPGN) pattern, and is principally caused by unrestricted activation of the complement alternative pathway. Genetic abnormalities of the complement system critically implicate in the pathogenesis of C3 glomerulopathy, but a systemic profile remains open, especially in Asia. Methods: In this study, we completed a comprehensive screen of 11 candidate alternative pathway genes by using targeted genomic enrichment and massively parallel sequencing on 43 patients with sporadic C3 glomerulopathy, which were classified as dense deposit disease (DDD; n = 10) and C3 glomerulonephritis (C3GN; n = 33) cases...
March 16, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29555686/brain-microvascular-endothelial-cells-exhibit-lower-activation-of-the-alternative-complement-pathway-than-glomerular-microvascular-endothelial-cells
#16
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, but 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...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29525453/expression-of-complement-receptor-3-cr3-and-regulatory-protein-cd46-on-dendritic-cells-of-antiretroviral-na%C3%A3-ve-and-treated-hiv-1-infected-individuals-correlation-with-immune-activation-status
#17
Nitesh Mishra, Madhav Mohata, Heena Aggarwal, Omkar Chaudhary, Bimal Kumar Das, Sanjeev Sinha, Anjali Hazarika, Kalpana Luthra
During infection and budding, human immunodeficiency virus-1 (HIV-1) acquires regulators of Complement Activation (RCAs) along with the host cell membrane on the viral envelope. Activation of host complement system results in opsonization of virus by complement fragments, however the virus evades complement mediated lysis (CoML) by virtue of the RCAs on the viral envelope. The RCAs on HIV-1 envelope process complement protein C3 into various fragments that promote viral entry and infection of cells through different complement receptors...
April 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29500241/statistical-validation-of-rare-complement-variants-provides-insights-into-the-molecular-basis-of-atypical-hemolytic-uremic-syndrome-and-c3-glomerulopathy
#18
Amy J Osborne, Matteo Breno, Nicolo Ghiringhelli Borsa, Fengxiao Bu, Véronique Frémeaux-Bacchi, Daniel P Gale, Lambertus P van den Heuvel, David Kavanagh, Marina Noris, Sheila Pinto, Pavithra M Rallapalli, Giuseppe Remuzzi, Santiago Rodríguez de Cordoba, Angela Ruiz, Richard J H Smith, Paula Vieira-Martins, Elena Volokhina, Valerie Wilson, Timothy H J Goodship, Stephen J Perkins
Atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) are associated with dysregulation and overactivation of the complement alternative pathway. Typically, gene analysis for aHUS and C3G is undertaken in small patient numbers, yet it is unclear which genes most frequently predispose to aHUS or C3G. Accordingly, we performed a six-center analysis of 610 rare genetic variants in 13 mostly complement genes ( CFH , CFI , CD46 , C3 , CFB , CFHR1 , CFHR3 , CFHR4 , CFHR5 , CFP , PLG , DGKE , and THBD ) from >3500 patients with aHUS and C3G...
April 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29492211/serum-complement-factor-i-is-associated-with-disease-activity-of-systemic-lupus-erythematosus
#19
Min-Hua Tseng, Shih-Hua Lin, Chao-Yi Wu, Hui-Ping Chien, Huang-Yu Yang, Yung-Chang Chen, Yu-Ching Chou, Jing-Long Huang
Although aberrant complement activation is involved in the pathogenesis of systemic lupus erythematosus (SLE), the role of complement regulatory proteins in disease activity of SLE remains limited. We enrolled the pediatric-onset SLE patients from our cohort study over 10 years. The clinical and laboratory data including SLEDAI disease activity score, and serum complement factor H (CFH), CFI, CD46, C5a, and C5b-9 in the active and remission phases were determined. Glomerular C5b-9 deposition as a complement activity marker was also examined...
February 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29447841/crispr-cas9-generated-human-cd46-cd55-and-cd59-knockout-cell-lines-as-a-tool-for-complement-research
#20
Astrid J F Thielen, Iris M van Baarsen, Marlieke L Jongsma, Sacha Zeerleder, Robbert M Spaapen, Diana Wouters
BACKGROUND: To prevent unwanted complement activation and subsequent damage, complement activation must be tightly regulated on healthy host cells. Dysregulation of the complement system contributes to the pathology of diseases like Paroxysmal Nocturnal Hemoglobinuria and atypical Hemolytic Uremic Syndrome. To investigate complement regulator deficiencies, primary patient cells may be used, but access to patient cells may be limited and cells are heterogeneous between different patients...
May 2018: Journal of Immunological Methods
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