The Complement System
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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. -
The Membrane Complement Regulatory Protein CD59 and Its Association with Rheumatoid Arthritis and Systemic Lupus Erythematosus
Current Medicine Research and Practice 9 (2019) 182e188 Contents lists available at ScienceDirect Current Medicine Research and Practice journal homepage: www.elsevier.com/locate/cmrp Review Article The membrane complement regulatory protein CD59 and its association with rheumatoid arthritis and systemic lupus erythematosus * Nibhriti Das a, Devyani Anand a, Bintili Biswas b, Deepa Kumari c, Monika Gandhi c, a Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India b Department of Zoology, Ramjas College, University of Delhi, India c University School of Biotechnology, Guru Gobind Singh Indraprastha University, India article info abstract Article history: The complement cascade consisting of about 50 soluble and cell surface proteins is activated in auto- Received 8 May 2019 immune inflammatory disorders. This contributes to the pathological manifestations in these diseases. In Accepted 30 July 2019 normal health, the soluble and membrane complement regulatory proteins protect the host against Available online 5 August 2019 complement-mediated self-tissue injury by controlling the extent of complement activation within the desired limits for the host's benefit. CD59 is a membrane complement regulatory protein that inhibits the Keywords: formation of the terminal complement complex or membrane attack complex (C5b6789n) which is CD59 generated on complement activation by any of the three pathways, namely, the classical, alternative, and RA SLE the mannose-binding lectin pathway. Animal experiments and human studies have suggested impor- Pathophysiology tance of membrane complement proteins including CD59 in the pathophysiology of rheumatoid arthritis Disease marker (RA) and systemic lupus erythematosus (SLE). Here is a brief review on CD59 and its distribution, structure, functions, and association with RA and SLE starting with a brief introduction on the com- plement system, its activation, the biological functions, and relations of membrane complement regu- latory proteins, especially CD59, with RA and SLE. -
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. -
More Than a Pore: Nonlytic Antimicrobial Functions of Downloaded from Complement and Bacterial Strategies for Evasion
REVIEW More than a Pore: Nonlytic Antimicrobial Functions of Downloaded from Complement and Bacterial Strategies for Evasion Elisabet Bjanes,a Victor Nizeta,b aDivision of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego, La Jolla, California, USA bSkaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California, USA http://mmbr.asm.org/ SUMMARY ........................................................................1 INTRODUCTION ...................................................................2 BY THE BOOK: CANONICAL COMPLEMENT CASCADES ...............................2 Off to the Races—Pathway Activation . 2 More and More—Amplification . 3 End of the Line—Termination . 3 Pump the Brakes—Inhibition . 5 Surviving MAC Attack—Evasion of Complement Lysis by Gram-Negative Bacteria . 6 NONLYTIC COMPLEMENT FUNCTIONS AND BACTERIAL EVASION MECHANISMS ......8 Special Considerations in Gram-Positive Bacteria . 8 on January 27, 2021 at UNIV OF CALIF SAN DIEGO Preparing the Meal—Complement Aids Opsonization and Phagocytosis . 8 Food for Thought—Complement Traffics to Autophagy . 10 Fueling the Fire—Complement Modulates Inflammatory Responses . 11 Casting a Wider NET—Complement and Neutrophil Synergy . 12 Inside Scoop—Novel Roles of Intracellular Complement . 13 Tying the Clot—Complement and Coagulation Cross Talk . 15 Bridging the Gap—Complement Instructs Adaptive Immunity . 17 REFRAMING SCIENTIFIC PARADIGMS AND THERAPEUTIC APPROACHES TO ENCOMPASS COMPLEMENT ..................................................18 -
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. -
Activation Regulates Alternative Pathway Complement Necrotic
Properdin Binds to Late Apoptotic and Necrotic Cells Independently of C3b and Regulates Alternative Pathway Complement Activation This information is current as of September 27, 2021. Wei Xu, Stefan P. Berger, Leendert A. Trouw, Hetty C. de Boer, Nicole Schlagwein, Chantal Mutsaers, Mohamed R. Daha and Cees van Kooten J Immunol 2008; 180:7613-7621; ; doi: 10.4049/jimmunol.180.11.7613 Downloaded from http://www.jimmunol.org/content/180/11/7613 References This article cites 56 articles, 27 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/180/11/7613.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 27, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Properdin Binds to Late Apoptotic and Necrotic Cells Independently of C3b and Regulates Alternative Pathway Complement Activation1,2 Wei Xu,* Stefan P. Berger,* Leendert A. -
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. -
Properdin Factor D: Effects on Thrombin-Induced Platelet Aggregation
Properdin factor D: effects on thrombin-induced platelet aggregation. A E Davis 3rd, D M Kenney J Clin Invest. 1979;64(3):721-728. https://doi.org/10.1172/JCI109515. Research Article Factor D, when preincubated with platelet suspensions, at concentrations as low as 1.2 micrograms/ml, inhibited thrombin-induced platelet aggregation. No inhibition of collagen or arachidonic acid-induced platelet aggregation was found. Inhibition occurred, but to a lesser extent, when thrombin and factor D were added to platelets at the same time. No inhibition occurred when factor D was added after thrombin. Thrombin was able to overcome inhibition by factor D by increasing its concentration. Diisopropyl-phosphorofluoridate-inactivated factor D also inhibited thrombin-induced platelet aggregation so that enzymatic activity of factor D was not required for inhibition. Factor D absorbed with hirudin coupled to Sepharose 6B showed no decrease in inhibitory capacity. 125I-Factor D bound to platelets in a manner suggesting an equilibrium reaction similar to thrombin. At low factor D input, binding was linear, whereas at higher input, binding began to approach saturation. Binding of 125I-labeled thrombin to platelets was inhibited by factor D. Analysis of these data show that factor D does not alter the total number of thrombin molecules which bind to the platelet surface at saturation. However, the dissociation constant for thrombin is altered from 2.78 to 6.90 nM in the presence of factor D (20 micrograms/ml). Factor D is thus a competitive inhibitor of thrombin binding, although the affinity of factor D for the platelet thrombin receptor is much less […] Find the latest version: https://jci.me/109515/pdf Properdin Factor D EFFECTS ON THROMBIN-INDUCED PLATELET AGGREGATION ALVIN E. -
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. -
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. -
By Map44 Pathway Activation in a Manner Inhibitable Pattern
Co-Complexes of MASP-1 and MASP-2 Associated with the Soluble Pattern-Recognition Molecules Drive Lectin Pathway Activation in a Manner Inhibitable This information is current as by MAp44 of September 28, 2021. Søren E. Degn, Lisbeth Jensen, Tomasz Olszowski, Jens C. Jensenius and Steffen Thiel J Immunol 2013; 191:1334-1345; Prepublished online 19 June 2013; Downloaded from doi: 10.4049/jimmunol.1300780 http://www.jimmunol.org/content/191/3/1334 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2013/06/19/jimmunol.130078 Material 0.DC1 References This article cites 43 articles, 23 of which you can access for free at: http://www.jimmunol.org/content/191/3/1334.full#ref-list-1 Why The JI? Submit online. by guest on September 28, 2021 • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Co-Complexes of MASP-1 and MASP-2 Associated with the Soluble Pattern-Recognition Molecules Drive Lectin Pathway Activation in a Manner Inhibitable by MAp44 Søren E. -
Opsonin-Dependent Stimulation of Bovine Neutrophil Oxidative Metabolism by Brucella Abortus Peter C
Veterinary Microbiology and Preventive Medicine Veterinary Microbiology and Preventive Medicine Publications 2-1988 Opsonin-dependent stimulation of bovine neutrophil oxidative metabolism by Brucella abortus Peter C. Canning U.S. Department of Agriculture Billy L. Deyoe U.S. Department of Agriculture James A. Roth Iowa State University, [email protected] Follow this and additional works at: https://lib.dr.iastate.edu/vmpm_pubs Part of the Veterinary Microbiology and Immunobiology Commons, Veterinary Preventive Medicine, Epidemiology, and Public Health Commons, and the Veterinary Toxicology and Pharmacology Commons The ompc lete bibliographic information for this item can be found at https://lib.dr.iastate.edu/ vmpm_pubs/190. For information on how to cite this item, please visit http://lib.dr.iastate.edu/ howtocite.html. This Article is brought to you for free and open access by the Veterinary Microbiology and Preventive Medicine at Iowa State University Digital Repository. It has been accepted for inclusion in Veterinary Microbiology and Preventive Medicine Publications by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Opsonin-dependent stimulation of bovine neutrophil oxidative metabolism by Brucella abortus Abstract Nonopsonized Brucella abortus and bacteria treated with fresh antiserum, heat-inactivated antiserum, or normal bovine serum were evaluated for their ability to stimulate production of superoxide anion and myeloperoxidasemediated iodination by neutrophils from cattle. Brucella abortus opsonized with fresh antiserum or beat-inactivated antiserum stimulated production of approximately 3 nmol of 0 2 -/106 neutrophils/30 min. Similarly treated bacteria also stimulated the binding of approximately 4.3 nmol of Nal/ 107 neutrophils/h to protein.