Expression of the Anaphylatoxin Receptors C3ar and C5ar Is Increased in Fatal Asthma
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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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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. -
BD Biosciences New RUO Reagents - November 2020
BD Biosciences New RUO reagents - November 2020 Reactivity Description Format Clone Size Cat. number Hu CD133 FITC W6B3C1 100µg 567029 Hu CD133 FITC W6B3C1 25µg 567033 Hu CD39 PE A1/CD39 100Tst 567156 Hu CD39 PE A1/CD39 25Tst 567157 Hu KIR2DL1/S1/S3/S5 PE HP-MA4 100Tst 567158 Hu KIR2DL1/S1/S3/S5 PE HP-MA4 25Tst 567159 Hu IL-22 Alexa Fluor® 647 MH22B2 100µg 567160 Hu IL-22 Alexa Fluor® 647 MH22B2 25µg 567161 Hu CD99 R718 TU12 50µg 751651 Hu CD161 R718 DX12 50µg 751652 Hu CD116 R718 HGMCSFR-M1 50µg 751653 Hu HLA-G R718 87G 50µg 751670 Hu CD27 R718 O323 50µg 751686 Hu CD80 (B7-1) R718 2D10.4 50µg 751737 Hu Integrin αvβ5 R718 ALULA 50µg 751738 Hu CD266 (Tweak-R) R718 ITEM-4 50µg 751739 Hu ErbB3 (HER-3) R718 SGP1 50µg 751799 Hu TCR Vβ5.1 R718 LC4 50µg 751816 Hu CD123 (IL-3Ra) R718 6H6 50µg 751844 Hu CD1a R718 SK9 50µg 751847 Hu CD20 R718 L27 50µg 751849 Hu Disial GD2 R718 14.G2A 50µg 751851 Reactivity Description Format Clone Size Cat. number Hu CD71 R718 L01.1 50µg 751853 Hu CD278 (ICOS) R718 DX29 50µg 751854 Hu B7-H4 R718 MIH43 50µg 751857 Hu CD53 R718 HI29 50µg 751858 Hu CD197 (CCR7) R718 2-L1-A 50µg 751859 Hu CD197 (CCR7) R718 3D12 50µg 751861 Hu CD31 R718 L133.1 50µg 751863 Hu EGF Receptor R718 EMAB-134 50µg 751864 Hu CD8b R718 2ST8.5H7 50µg 751867 Hu CD31 R718 MBC 78.2 50µg 751869 Hu CD162 R718 KPL-1 50µg 751873 Hu CD24 R718 ML5 50µg 751874 Hu CD159C (NKG2C) R718 134591 50µg 751876 Hu CD169 (Siglec-1) R718 7-239 50µg 751877 Hu CD16b R718 CLB-GRAN11.5 50µg 751880 Hu IgM R718 UCH-B1 50µg 751881 Hu CD275 R718 2D3/B7-H2 50µg 751883 Hu CD307e -
Neutrophil Chemoattractant Receptors in Health and Disease: Double-Edged Swords
Cellular & Molecular Immunology www.nature.com/cmi REVIEW ARTICLE Neutrophil chemoattractant receptors in health and disease: double-edged swords Mieke Metzemaekers1, Mieke Gouwy1 and Paul Proost 1 Neutrophils are frontline cells of the innate immune system. These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential. Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis, for inflammation modulation and resolution, wound healing and tissue repair. After fulfilling the appropriate effector functions, however, dampening neutrophil activation and infiltration is crucial to prevent damage to the host. In humans, chemoattractant molecules can be categorized into four biochemical families, i.e., chemotactic lipids, formyl peptides, complement anaphylatoxins and chemokines. They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs. Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors (GPCRs). In addition, emerging evidence suggests an important role for atypical chemoattractant receptors (ACKRs) that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses. The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation, with a pivotal modulatory role for the (inflammatory) environment. Here, we provide an overview -
Blood Cell Changes in Complement Activation- Related Pseudoallergy
Eur. J. Nanomed. 2015; 7(3): 233–244 Mini Review Zsófia Patkó* and János Szebeni Blood cell changes in complement activation- related pseudoallergy DOI 10.1515/ejnm-2015-0021 Introduction Received April 13, 2015; accepted May 19, 2015 Complement activation-related pseudoallergy (CARPA), as the name implies, is a non-Ig-E-mediated (pseudo- Abstract: The characteristic physiological changes allergic) hypersensitivity reaction (HSR) that is triggered in complement (C) activation-related pseudoallergy by C activation, or C activation plays a major contributing (CARPA) include thrombocytopenia, leukocytosis and role. CARPA is best known in the context of nanotoxicity, leukopenia with or without compensatory leukocytosis. since nanomedicines, i.e. particulate drugs and agents in In the background of these phenomena it is known that the nano (10−9–10 −6 m) size range often cause such reac- anaphylatoxins, the triggers of CARPA, can activate white tions. As reviewed earlier (1–8), and also discussed in blood cells (WBCs) and platelets, and that this activation other papers of this issue, the phenomenon represents can lead to the binding of these cells to each other and an immune barrier to the clinical use of many promising also to capillary endothelial cells, entailing microthrom- nanomedicines. In essence, CARPA may be perceived as bus formation and circulatory blockage mainly in the pul- a biological stress on blood that arises as a consequence monary and coronary microcirculation. These changes of the similarity of nanomedicines to viruses, between are key contributors to the hemodynamic alterations in which the immune system cannot make difference (8). CARPA, and can lead to anaphylactic shock. -
Host-Parasite Interaction of Atlantic Salmon (Salmo Salar) and the Ectoparasite Neoparamoeba Perurans in Amoebic Gill Disease
ORIGINAL RESEARCH published: 31 May 2021 doi: 10.3389/fimmu.2021.672700 Host-Parasite Interaction of Atlantic salmon (Salmo salar) and the Ectoparasite Neoparamoeba perurans in Amoebic Gill Disease † Natasha A. Botwright 1*, Amin R. Mohamed 1 , Joel Slinger 2, Paula C. Lima 1 and James W. Wynne 3 1 Livestock and Aquaculture, CSIRO Agriculture and Food, St Lucia, QLD, Australia, 2 Livestock and Aquaculture, CSIRO Agriculture and Food, Woorim, QLD, Australia, 3 Livestock and Aquaculture, CSIRO Agriculture and Food, Hobart, TAS, Australia Marine farmed Atlantic salmon (Salmo salar) are susceptible to recurrent amoebic gill disease Edited by: (AGD) caused by the ectoparasite Neoparamoeba perurans over the growout production Samuel A. M. Martin, University of Aberdeen, cycle. The parasite elicits a highly localized response within the gill epithelium resulting in United Kingdom multifocal mucoid patches at the site of parasite attachment. This host-parasite response Reviewed by: drives a complex immune reaction, which remains poorly understood. To generate a model Diego Robledo, for host-parasite interaction during pathogenesis of AGD in Atlantic salmon the local (gill) and University of Edinburgh, United Kingdom systemic transcriptomic response in the host, and the parasite during AGD pathogenesis was Maria K. Dahle, explored. A dual RNA-seq approach together with differential gene expression and system- Norwegian Veterinary Institute (NVI), Norway wide statistical analyses of gene and transcription factor networks was employed. A multi- *Correspondence: tissue transcriptomic data set was generated from the gill (including both lesioned and non- Natasha A. Botwright lesioned tissue), head kidney and spleen tissues naïve and AGD-affected Atlantic salmon [email protected] sourced from an in vivo AGD challenge trial. -
The Complement System: a Powerful Modulator and Effector of Astrocyte Function in the Healthy and Diseased Central Nervous System
cells Review The Complement System: A Powerful Modulator and Effector of Astrocyte Function in the Healthy and Diseased Central Nervous System Marcela Pekna 1,3,4,* and Milos Pekny 2,3,4 1 Laboratory of Regenerative Neuroimmunology, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 40530 Gothenburg, Sweden 2 Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 40530 Gothenburg, Sweden; [email protected] 3 Florey Institute of Neuroscience and Mental Health, Parkville, Melbourne 3010, Australia 4 School of Medicine and Public Health, University of Newcastle, Newcastle 2308, Australia * Correspondence: [email protected]; Tel.: +46-31-786-3581 Abstract: The complement system, an effector arm of the innate immune system that plays a critical role in tissue inflammation, the elimination of pathogens and the clearance of dead cells and cell debris, has emerged as a regulator of many processes in the central nervous system, including neural cell genesis and migration, control of synapse number and function, and modulation of glial cell responses. Complement dysfunction has also been put forward as a major contributor to neurological disease. Astrocytes are neuroectoderm-derived glial cells that maintain water and ionic homeostasis, and control cerebral blood flow and multiple aspects of neuronal functioning. By virtue of their Citation: Pekna, M.; Pekny, M. The Complement System: A Powerful expression of soluble as well as membrane-bound complement proteins and receptors, astrocytes are Modulator and Effector of Astrocyte able to both send and receive complement-related signals. -
An Unexpected Role for the Anaphylatoxin C5a Receptor in Allergic Sensitization Bart N
commentaries fied mice with minimal or no steady-state Phone: (314) 362-8834; Fax: (314) 362-8826; 7. Socolovsky, M., et al. 2001. Ineffective erythropoie- sis in Stat5a(–/–)5b(–/–) mice due to decreased sur- phenotype. In many ways these mice could E-mail: [email protected]. vival of early erythroblasts. Blood. 98:3261–3273. be viewed as models for otherwise normal 8. Zang, H., et al. 2001. The distal region and receptor adult humans who exhibit exaggerated or 1. Palis, J., and Segel, G.B. 1998. Developmental biol- tyrosines of the Epo receptor are non-essential for ogy of erythropoiesis. Blood Rev. 12:106–114. in vivo erythropoiesis. EMBO J. 20:3156–3166. unexpected responses to inflammation, 2. Obinata, M., and Yanai, N. 1999. Cellular and 9. D’Andrea, A.D., et al. 1991. The cytoplasmic region infectious agents, or cancer progression. molecular regulation of an erythropoietic induc- of the erythropoietin receptor contains nonover- As such, they have the potential to identify tive microenvironment (EIM). Cell Struct. Funct. lapping positive and negative growth-regulatory 24:171–179. and dissect regulatory pathways that influ- domains. Mol. Cell. Biol. 11:1980–1987. 3. Menon, M.P., et al. 2006. Signals for stress erythro- 10. Wagner, K.U., et al. 2000. Conditional deletion of the ence but do not cause disease. poiesis are integrated via an erythropoietin receptor– Bcl-x gene from erythroid cells results in hemolytic phosphotyrosine-343–Stat5 axis. J. Clin. Invest. anemia and profound splenomegaly. Development. Acknowledgments 116:683–694. doi:10.1172/JCI25227. 127:4949–4958. 4. Teglund, S., et al. -
An Overview on G Protein-Coupled Receptor-Induced Signal Transduction in Acute Myeloid Leukemia
An overview on G protein-coupled receptor-induced signal transduction in Acute Myeloid Leukemia 1* 1,3 4,5,6 2* Frode Selheim , Elise Aasebø , Catalina Ribas and Anna M. Aragay 1The Proteomics Unit at the University of Bergen, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5020 Bergen, Norway; 3 Department of Clinical Science, University of Bergen, Jonas Lies vei 87, 5021 Bergen, Norway; [email protected]. 2Departamento de Biologia Celular. Instituto de Biología Molecular de Barcelona (IBMB-CSIC), Spanish National Research Council (CSIC), Baldiri i Reixac, 15, 08028 Barcelona, Spain; [email protected]. 4Departamento de Biología Molecular and Centro de Biología Molecular “Severo Ochoa” (UAM-CSIC), 28049 Madrid, Spain; 5Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain; 6CIBER de Enfermedades Cardiovasculares, ISCIII (CIBERCV), 28029 Madrid, Spain, [email protected] * Corresponding authors: Frode Selheim Adr: Jonas Lies vei 91, 5020 Bergen, Norway Email: [email protected], Tel:+4755586091 Anna M. Aragay Adr: Baldiri i Reixac, 15, 08028 Barcelona. Spain. E-mail: [email protected]; Tel.: +934098671 1 Abstract Background: Acute myeloid leukemia (AML) is a genetically heterogeneous disease characterized by uncontrolled proliferation of precursor myeloid-lineage cells in the bone marrow. AML is also characterized with patients with poor long-term survival outcomes due to relapse. Many efforts have been made to understand the biological heterogeneity of AML and the challenges to develop new therapies are therefore enormous. G protein-coupled receptors (GPCRs) are a large attractive drug targeted family of transmembrane proteins, and aberrant GPCR expression and GPCR-mediated signaling have been implicated in leukemogenesis of AML. -
G Protein-Coupled Receptors
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. British Journal of Pharmacology (2015) 172, 5744–5869 THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: G protein-coupled receptors Stephen PH Alexander1, Anthony P Davenport2, Eamonn Kelly3, Neil Marrion3, John A Peters4, Helen E Benson5, Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5 and CGTP Collaborators 1School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK, 2Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK, 3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK, 4Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK, 5Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/ 10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. -
G Protein‐Coupled Receptors
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. British Journal of Pharmacology (2019) 176, S21–S141 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors Stephen PH Alexander1 , Arthur Christopoulos2 , Anthony P Davenport3 , Eamonn Kelly4, Alistair Mathie5 , John A Peters6 , Emma L Veale5 ,JaneFArmstrong7 , Elena Faccenda7 ,SimonDHarding7 ,AdamJPawson7 , Joanna L Sharman7 , Christopher Southan7 , Jamie A Davies7 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria 3052, Australia 3Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK 4School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 5Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 6Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 7Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. -
ANAPHYLATOXIN-MEDIATED REGULATION of the IMMUNE RESPONSE I. C3a-Mediated Suppression of Human and Murine Humoral Immune Responses*
ANAPHYLATOXIN-MEDIATED REGULATION OF THE IMMUNE RESPONSE I. C3a-mediated Suppression of Human and Murine Humoral Immune Responses* By EDWARD L. MORGAN,~ WILLIAM O. WEIGLE,§ AND TONY E. HUGLI[I From the Department of Immunopathology and Department of Molecular Immunology Scripps Clinic and Downloaded from http://rupress.org/jem/article-pdf/155/5/1412/1092540/1412.pdf by guest on 26 September 2021 Research Foundation La Jolla, California 92037 Regulation of the immune response by the third component of complement (C3) has been extensively investigated. C3 and the cleavage products C3b, C3c, and C3d have each received considerable attention in studies of lymphocyte activation and regulation (1-12). Receptors for fragments of C3--such as C3b, C3c, and C3d--have been detected on a number of cells including lymphocytes and macrophages. However, the biological significance of these receptors remains unknown. C3 has been implicated in the activation of macrophages (8) and in modulation of cellular immune functions (1-17). Most of these biological activities have been attributed to C3b, C3c, or C3d with little or no activity associated with the C3a fragment (5, 7). The C3a fragment has anaphylatoxin properties as evidenced by its potent spas- mogenic and tachyphylactic action (17). More recently, Needleman et al. (18) reported that in a serum-free environment, a C3 fragment, presumably C3a, suppresses the antigen- and mitogen-induced proliferative responses of human peripheral blood lymphocytes (PBL). Normal control of C3a action is governed by a serum enzyme (17). Interaction of C3a with endogenous carboxypeptidase N results in the rapid cleavage of the terminal arginine from C3a producing C3ades Ars-77. -
Novel Therapies for Eosinophilic Disorders
Novel Therapies for Eosinophilic Disorders Bruce S. Bochner, MD KEYWORDS Eosinophil Therapies Antibodies Targets Pharmacology Biomarkers KEY POINTS A sizable unmet need exists for new, safe, selective, and effective treatments for eosinophil-associated diseases, such as hypereosinophilic syndrome, eosinophilic gastrointestinal disorders, nasal polyposis, and severe asthma. An improved panel of biomarkers to help guide diagnosis, treatment, and assessment of disease activity is also needed. An impressive array of novel therapeutic agents, including small molecules and biologics, that directly or indirectly target eosinophils and eosinophilic inflammation are undergoing controlled clinical trials, with many already showing promising results. A large list of additional eosinophil-related potential therapeutic targets remains to be pursued, including cell surface structures, soluble proteins that influence eosinophil biology, and eosinophil-derived mediators that have the potential to contribute adversely to disease pathophysiology. INTRODUCTION Eosinophilic disorders, also referred to as eosinophil-associated diseases, consist of a range of infrequent conditions affecting virtually any body compartment and organ.1 The most commonly affected areas include the bone marrow, blood, mucosal sur- faces, and skin, often with immense disease- and treatment-related morbidity, Disclosure Statement: Dr Bochner’s research efforts are supported by grants AI072265, AI097073 and HL107151 from the National Institutes of Health. He has current or recent consul- ting or scientific advisory board arrangements with, or has received honoraria from, Sanofi-A- ventis, Pfizer, Svelte Medical Systems, Biogen Idec, TEVA, and Allakos, Inc. and owns stock in Allakos, Inc. and Glycomimetics, Inc. He receives publication-related royalty payments from Elsevier and UpToDate and is a coinventor on existing and pending Siglec-8-related patents and, thus, may be entitled to a share of future royalties received by Johns Hopkins University on the potential sales of such products.