Complement Receptor CD46 Co-Stimulates Optimal Human CD8 T
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(CD147) Is Induced by C/Ebpβ and Is Differentially Expressed in ALK+
Laboratory Investigation (2017) 97, 1095–1102 © 2017 USCAP, Inc All rights reserved 0023-6837/17 EMMPRIN (CD147) is induced by C/EBPβ and is differentially expressed in ALK+ and ALK − anaplastic large-cell lymphoma Janine Schmidt1, Irina Bonzheim1, Julia Steinhilber1, Ivonne A Montes-Mojarro1, Carlos Ortiz-Hidalgo2, Wolfram Klapper3, Falko Fend1 and Leticia Quintanilla-Martínez1 Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is characterized by expression of oncogenic ALK fusion proteins due to the translocation t(2;5)(p23;q35) or variants. Although genotypically a T-cell lymphoma, ALK+ ALCL cells frequently show loss of T-cell-specific surface antigens and expression of monocytic markers. C/EBPβ, a transcription factor constitutively overexpressed in ALK+ ALCL cells, has been shown to play an important role in the activation and differentiation of macrophages and is furthermore capable of transdifferentiating B-cell and T-cell progenitors to macrophages in vitro. To analyze the role of C/EBPβ for the unusual phenotype of ALK+ ALCL cells, C/EBPβ was knocked down by RNA interference in two ALK+ ALCL cell lines, and surface antigen expression profiles of these cell lines were generated using a Human Cell Surface Marker Screening Panel (BD Biosciences). Interesting candidate antigens were further analyzed by immunohistochemistry in primary ALCL ALK+ and ALK − cases. Antigen expression profiling revealed marked changes in the expression of the activation markers CD25, CD30, CD98, CD147, and CD227 after C/EBPβ knockdown. Immunohistochemical analysis confirmed a strong, membranous CD147 (EMMPRIN) expression in ALK+ ALCL cases. In contrast, ALK − ALCL cases showed a weaker CD147 expression. -
CD46 Expression Is Indicative of Shorter Revival-Free Survival for Ovarian Cancer Patients
ANTICANCER RESEARCH 26: 4943-4948 (2006) CD46 Expression is Indicative of Shorter Revival-free Survival for Ovarian Cancer Patients PAWEL SUROWIAK1,2,3, VERENA MATERNA1, ADAM MACIEJCZYK3, IRINA KAPLENKO4, MAREK SPACZYNSKI4, MANFRED DIETEL1, HERMANN LAGE1 and MACIEJ ZABEL2,5 1Institute of Pathology, Charité Campus Mitte, D-10117 Berlin, Germany; 2Chair and Department of Histology and Embryology, University School of Medicine, ul. Chalubinskiego 6a, 50-356 Wroclaw; 3Lower Silesian Centre of Oncology, pl. Hirszfelda 12, 53-413 Wroclaw; 4Chair and Department of Obstetrics and Gynaecology and 5Chair and Department of Histology and Embryology, University School of Medicine, ul. Swiecickiego 6, 60-781 Poznan, Poland Abstract. Background: The membrane cofactor protein CD46 cure very rarely. Despite the introduction of novel represents a complement inhibitor, which protects autologous chemotherapy regimens, the frequency of 5 - year survival cells from complement - mediated cytotoxicity. CD46 may of patients at all clinical stages has not exceeded 40%, in the exhibit the potential to protect tumor cells from the immune last 20 years (2). Therefore, intense efforts are being made responses of the host. The present study aimed to evaluate the in numerous centres to detect new prognostic factors, which prognostic significance of CD46 expression in ovarian cancers. might prove valuable towards studies on new therapeutic Materials and Methods: The analyses were performed on 73 approaches. ovarian cancer samples. Immunohistochemical reactions were The absence of the host’s immune response to the performed on paraffin sections of tumors using monoclonal presence of tumor cells represents one of the circumstances, antibodies directed against CD46. The immunohistochemical which promotes development of the tumor. -
Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse
Welcome to More Choice CD Marker Handbook For more information, please visit: Human bdbiosciences.com/eu/go/humancdmarkers Mouse bdbiosciences.com/eu/go/mousecdmarkers Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse CD3 CD3 CD (cluster of differentiation) molecules are cell surface markers T Cell CD4 CD4 useful for the identification and characterization of leukocytes. The CD CD8 CD8 nomenclature was developed and is maintained through the HLDA (Human Leukocyte Differentiation Antigens) workshop started in 1982. CD45R/B220 CD19 CD19 The goal is to provide standardization of monoclonal antibodies to B Cell CD20 CD22 (B cell activation marker) human antigens across laboratories. To characterize or “workshop” the antibodies, multiple laboratories carry out blind analyses of antibodies. These results independently validate antibody specificity. CD11c CD11c Dendritic Cell CD123 CD123 While the CD nomenclature has been developed for use with human antigens, it is applied to corresponding mouse antigens as well as antigens from other species. However, the mouse and other species NK Cell CD56 CD335 (NKp46) antibodies are not tested by HLDA. Human CD markers were reviewed by the HLDA. New CD markers Stem Cell/ CD34 CD34 were established at the HLDA9 meeting held in Barcelona in 2010. For Precursor hematopoetic stem cell only hematopoetic stem cell only additional information and CD markers please visit www.hcdm.org. Macrophage/ CD14 CD11b/ Mac-1 Monocyte CD33 Ly-71 (F4/80) CD66b Granulocyte CD66b Gr-1/Ly6G Ly6C CD41 CD41 CD61 (Integrin b3) CD61 Platelet CD9 CD62 CD62P (activated platelets) CD235a CD235a Erythrocyte Ter-119 CD146 MECA-32 CD106 CD146 Endothelial Cell CD31 CD62E (activated endothelial cells) Epithelial Cell CD236 CD326 (EPCAM1) For Research Use Only. -
C3b Catalog Number: A114 Sizes Available
Name: C3b Catalog Number: A114 Sizes Available: 250 µg/vial Concentration: 1.0 mg/mL (see Certificate of Analysis for actual concentration) Form: Liquid Purity: >90% by SDS-PAGE Buffer: 10 mM sodium phosphate, 145 mM NaCl, pH 7.3 Extinction Coeff. A280 nm = 1.03 at 1.0 mg/mL Molecular Weight: 176,000 Da (2 chains) Preservative: None, 0.22 µm filtered Storage: -70oC or below. Avoid freeze/thaw. Source: Normal human serum (shown by certified tests to be negative for HBsAg and for antibodies to HCV, HIV-1 and HIV-II). Precautions: Use normal precautions for handling human blood products. Origin: Manufactured in the USA. General Description C3b is derived from native C3 upon cleavage and release of C3a. It is prepared by cleavage with the alternative pathway C3 convertase. This is important because only a single bond in C3 is cleaved by the native convertase, while cleavage by other proteases, such as trypsin, results in multiple cleavages at many other sites in the protein. Native human C3b is a glycosylated (~2.8%) polypeptide containing two disulfide-linked chains. C3b is central to the function of all three pathways of complement (Law, S.K.A. and Reid, K.B.M. (1995)). Initiation of each pathway generates proteolytic enzyme complexes (C3 convertases) which are bound to the target surface. These enzymes cleave a peptide bond in C3 releasing the anaphylatoxin C3a and activating C3b. For a brief time (~60 µs) this nascent C3b is capable of reacting with and covalently coupling to hydroxyl groups on the target surface. -
Complement Recognition Pathways in Renal Transplantation
BRIEF REVIEW www.jasn.org Complement Recognition Pathways in Renal Transplantation Christopher L. Nauser, Conrad A. Farrar, and Steven H. Sacks Medical Research Council Centre for Transplantation, Division of Transplantation Immunology and Mucosal Biology, King’s College London, National Health Service Guy’s and St. Thomas’ Trust, London, United Kingdom ABSTRACT The complement system, consisting of soluble and cell membrane–bound compo- weigh its effect on organ injury and nents of the innate immune system, has defined roles in the pathophysiology of renal rejection with dampening the antimi- allograft rejection. Notably, the unavoidable ischemia-reperfusion injury inherent to crobial functions of the complement sys- transplantation is mediated through the terminal complement activation products tem, such as opsonisation, cell lysis, and C5a and C5b-9. Furthermore, biologically active fragments C3a and C5a, produced recruitment of neutrophils and other in- during complement activation, can modulate both antigen presentation and T cell flammatory cells.7 It is our belief that priming, ultimately leading to allograft rejection. Earlier work identified renal tubule therapeutic strategies can be designed cell synthesis of C3, rather than hepatic synthesis of C3, as the primary source of C3 to specificallytargetthekeyinitiators driving these effects. Recent efforts have focused on identifying the local triggers of of complement activation at the relevant complement activation. Collectin-11, a soluble C-type lectin expressed in renal tis- location, such as complement-binding sue, has been implicated as an important trigger of complement activation in renal anti-HLA antibodies in the vascular tissue. In particular, collectin-11 has been shown to engage L-fucose at sites of compartment or the initiator(s) of local ischemic stress, activating the lectin complement pathway and directing the innate complement activation in the extravas- immune response to the distressed renal tubule. -
Blocking Properdin Prevents Complement-Mediated Hemolytic Uremic Syndrome and Systemic Thrombophilia
BASIC RESEARCH www.jasn.org Blocking Properdin Prevents Complement-Mediated Hemolytic Uremic Syndrome and Systemic Thrombophilia Yoshiyasu Ueda,1 Takashi Miwa,1 Damodar Gullipalli,1 Sayaka Sato,1 Daisuke Ito,1 Hangsoo Kim,1 Matthew Palmer,2 and Wen-Chao Song1 Departments of 1Systems Pharmacology and Translational Therapeutics and 2Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania ABSTRACT Background Properdin (P) is a positive regulator of the alternative pathway of complement activation. Although P inhibition is expected and has been shown to ameliorate the alternative pathway of comple- ment-mediated tissue injury in several disease models, it unexpectedly exacerbated renal injury in a murine model of C3 glomerulopathy. The role of P in atypical hemolytic uremic syndrome (aHUS) is uncertain. Methods We blocked P function by genetic deletion or mAb-mediated inhibition in mice carrying a factor H (FH) point mutation, W1206R (FHR/R), that causes aHUS and systemic thrombophilia with high mortality. Results Pdeficiency completely rescued FHR/R mice from premature death and prevented thrombocyto- penia, hemolytic anemia, and renal disease. It also eliminated macrovessel thrombi that were prevalent in FHR/R mice. All mice that received a function-blocking anti-P mAb for 8 weeks survived the experimental period and appeared grossly healthy. Platelet counts and hemoglobin levels were significantly improved in FHR/R mice after 4 weeks of anti-P mAb treatment. One half of the FHR/R mice treated with an isotype control mAb but none of the anti-P mAb-treated mice developed stroke-related neurologic disease. Anti-P mAb-treated FHR/R mice showed largely normal renal histology, and residual liver thrombi were detected in only three of 15 treated mice. -
Complement Component 3 (C3) Concentrations in Cancer Patients: a Systematic Review and Meta-Analysis
Complement Component 3 (C3) Concentrations in Cancer Patients: A Systematic Review and Meta-Analysis Zipeng Yang South China Agricultural University Zi-Guo Yuan ( [email protected] ) Anqun Yang Dapeng New District Nan'ao Peolple's Hospital of Shenzhen, Guangdong Province, China Xiu-Xiang Zhang South China Agricultural University College of Agriculture Xiaohu Wang Guangdong Academy of Agricultural Sciences, Guangzhou, Guangdong Province Miao Yu Dongfeng Xiyuan District, Stomatological Hospital Aliated to Guangzhou Medical University, Guangzhou Yasser S.Mahmmod Zagazig University Jorge A Hernandez University of Florida Zhaowen Ren South China Agricultural University Xirui Zhang South China Agricultural University Wei Cong Shandong University Research article Keywords: Complement Component 3, Cancer Patients, Meta-Analysis Posted Date: March 26th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-18256/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/17 Abstract Background The aim of this study was to investigate the association between the serum complement component 3 “C3” level and the patients with different types of cancer. Our study nding would ultimately provide reliable scientic conclusions to guide clinical practice. Methods PubMed, Embase, The Chorane Library and Google Scholar were systematically searched to identify all studies on serum C3 concentrations in cancer patients published as of September 2019. Additionally, we conducted a clinical study on serum C3 in lung cancer patients and healthy people. The levels of serum complement C3 in 84 lung cancer patients and 30 healthy people were examined by ELISA. We used standardized mean differences (SMD) to report the pooled estimation, and I² statistics were calculated to examine the heterogeneity. -
Stelios Pavlidis3, Matthew Loza3, Fred Baribaud3, Anthony
Supplementary Data Th2 and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in UBIOPRED Chih-Hsi Scott Kuo1.2, Stelios Pavlidis3, Matthew Loza3, Fred Baribaud3, Anthony Rowe3, Iaonnis Pandis2, Ana Sousa4, Julie Corfield5, Ratko Djukanovic6, Rene 7 7 8 2 1† Lutter , Peter J. Sterk , Charles Auffray , Yike Guo , Ian M. Adcock & Kian Fan 1†* # Chung on behalf of the U-BIOPRED consortium project team 1Airways Disease, National Heart & Lung Institute, Imperial College London, & Biomedical Research Unit, Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom; 2Department of Computing & Data Science Institute, Imperial College London, United Kingdom; 3Janssen Research and Development, High Wycombe, Buckinghamshire, United Kingdom; 4Respiratory Therapeutic Unit, GSK, Stockley Park, United Kingdom; 5AstraZeneca R&D Molndal, Sweden and Areteva R&D, Nottingham, United Kingdom; 6Faculty of Medicine, Southampton University, Southampton, United Kingdom; 7Faculty of Medicine, University of Amsterdam, Amsterdam, Netherlands; 8European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, France. †Contributed equally #Consortium project team members are listed under Supplementary 1 Materials *To whom correspondence should be addressed: [email protected] 2 List of the U-BIOPRED Consortium project team members Uruj Hoda & Christos Rossios, Airways Disease, National Heart & Lung Institute, Imperial College London, UK & Biomedical Research Unit, Biomedical Research Unit, Royal -
B-Cell Receptor Pathway Inhibitors Affect CD20 Levels and Impair Antitumor Activity of Anti-CD20 Monoclonal Antibodies
Letters to the Editor 1163 13 Kuruvilla J, Gutierrez M, Shah BD, Gabrail NY, de Nully Brown P, 14 Yu L, Mohamed AJ, Simonson OE, Vargas L, Blomberg KE, Bjorkstrand B et al. Stone RM et al. Preliminary evidence of anti tumor activity of selinexor Proteasome-dependent autoregulation of Bruton tyrosine kinase (Btk) promoter (KPT-330) in a phase I trial of a first-in-class oral selective inhibitor via NF-kappaB. Blood 2008; 111: 4617–4626. of nuclear export (SINE) in patients (pts) with relapsed/refractory non 15BurgerJA,BurgerM,KippsTJ.Chronic lymphocytic leukemia B cells Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Blood 2013; express functional CXCR4 chemokine receptors that mediate spontaneous 122: 90. migration beneath bone marrow stromal cells. Blood 1999; 94: 3658–3667. Supplementary Information accompanies this paper on the Leukemia website (http://www.nature.com/leu) B-cell receptor pathway inhibitors affect CD20 levels and impair antitumor activity of anti-CD20 monoclonal antibodies Leukemia (2014) 28, 1163–1167; doi:10.1038/leu.2014.12 also tested a primary MCL sample and upon treatment with BCR inhibitors observed a significant downregulation of surface CD20 levels and a trend towards impaired R-CDC and O-CDC (Supplementary Figure 1b). Moreover, we determined the Signaling via the aberrantly activated B-cell receptor (BCR) has a influence of BCR inhibitors on CD20 surface levels in a critical role in the pathogenesis of B-cell tumors by promoting series of 15 tumor cell lines, including Burkitt’s lymphoma (Ramos, survival and clonal expansion of malignant B cells.1,2 Multiple Daudi and BJAB), ALL (NALM-6), diffuse large B-cell lymphoma preclinical studies indicate that blocking various components of (BCR-dependent Ly-1, Ly-7, Ly-10, DHL-6, HBL-1, U2932 and the BCR signaling pathway holds a great therapeutic potential in BCR-independent Ly-4, Ly-19, Pfeiffer) and CLL (EHEB and MEC-1). -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
The 'C3ar Antagonist' SB290157 Is a Partial C5ar2 Agonist
bioRxiv preprint doi: https://doi.org/10.1101/2020.08.01.232090; this version posted August 3, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The ‘C3aR antagonist’ SB290157 is a partial C5aR2 agonist Xaria X. Li1, Vinod Kumar1, John D. Lee1, Trent M. Woodruff1* 1School of Biomedical Sciences, The University of Queensland, St Lucia, 4072 Australia. * Correspondence: Prof. Trent M. Woodruff School of Biomedical Sciences, The University of Queensland, St Lucia, 4072 Australia. Ph: +61 7 3365 2924; Fax: +61 7 3365 1766; E-mail: [email protected] Keywords: Complement C3a, C3aR, SB290157, C5aR1, C5aR2 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.01.232090; this version posted August 3, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abbreviations used in this article: BRET, bioluminescence resonance energy transfer; BSA, bovine serum albumin; C3aR, C3a receptor C5aR1, C5a receptor 1; CHO-C3aR, Chinese hamster ovary cells stably expressing C3aR; CHO-C5aR1, Chinese hamster ovary cells stably expressing C5aR1; DMEM, Dulbecco's Modified Eagle's Medium; ERK1/2, extracellular signal-regulated kinase 1/2; FBS, foetal bovine serum; HEK293, human embryonic kidney 293 cells; HMDM, human monocyte-derived macrophage; i.p., intraperitoneal; i.v., intravenous; rhC5a, recombinant human C5a; RT, room temperature; S.E.M. -
An Anticomplement Agent That Homes to the Damaged Brain and Promotes Recovery After Traumatic Brain Injury in Mice
An anticomplement agent that homes to the damaged brain and promotes recovery after traumatic brain injury in mice Marieta M. Rusevaa,1,2, Valeria Ramagliab,1, B. Paul Morgana, and Claire L. Harrisa,3 aInstitute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom; and bDepartment of Genome Analysis, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands Edited by Douglas T. Fearon, Cornell University, Cambridge, United Kingdom, and approved September 29, 2015 (received for review July 15, 2015) Activation of complement is a key determinant of neuropathology to rapidly and specifically inhibit MAC at sites of complement and disability after traumatic brain injury (TBI), and inhibition is activation, and test its therapeutic potential in experimental TBI. neuroprotective. However, systemic complement is essential to The construct, termed CD59-2a-CRIg, comprises CD59a linked fight infections, a critical complication of TBI. We describe a to CRIg via the murine IgG2a hinge. CD59a prevents assembly targeted complement inhibitor, comprising complement receptor of MAC in cell membranes (16), whereas CRIg binds C3b/iC3b of the Ig superfamily (CRIg) fused with complement regulator CD59a, deposited at sites of complement activation (17). The IgG2a designed to inhibit membrane attack complex (MAC) assembly at hinge promotes dimerization to increase ligand avidity. CD59- sites of C3b/iC3b deposition. CRIg and CD59a were linked via the 2a-CRIg protected in the TBI model, demonstrating that site- IgG2a hinge, yielding CD59-2a-CRIg dimer with increased iC3b/C3b targeted anti-MAC therapeutics may be effective in prevention binding avidity and MAC inhibitory activity. CD59-2a-CRIg inhibited of secondary neuropathology and improve neurologic recovery MAC formation and prevented complement-mediated lysis in vitro.