C5

Summary

Gene Symbol: C5
Description: complement C5
Alias: C5D, C5a, C5b, CPAMD4, ECLZB, complement C5, C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4, C5a anaphylatoxin, anaphylatoxin C5a analog, complement component 5, prepro-C5
Species: human

Top Publications

  1. doi Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus
    E Y M G Fung
    Juvenile Diabetes Research Foundation Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    Genes Immun 10:188-91. 2009
  2. pmc TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study
    Robert M Plenge
    Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA, USA
    N Engl J Med 357:1199-209. 2007
  3. pmc A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis
    Fina A S Kurreeman
    Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
    PLoS Med 4:e278. 2007
  4. doi Association of the TRAF1-C5 locus on chromosome 9 with juvenile idiopathic arthritis
    Edward M Behrens
    The Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Arthritis Rheum 58:2206-7. 2008
  5. doi Association of the TRAF1/C5 locus with increased mortality, particularly from malignancy or sepsis, in patients with rheumatoid arthritis
    Vasileios F Panoulas
    Dudley Group of Hospitals National Health Service Trust, Dudley, UK
    Arthritis Rheum 60:39-46. 2009
  6. pmc Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations
    Hye Soon Lee
    Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Seoul, South Korea
    Arthritis Rheum 60:364-71. 2009
  7. doi Susceptibility variants for rheumatoid arthritis in the TRAF1-C5 and 6q23 loci: a meta-analysis
    Nikolaos A Patsopoulos
    Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
    Ann Rheum Dis 69:561-6. 2010
  8. doi Single nucleotide polymorphisms of complement component 5 and periodontitis
    L Chai
    Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
    J Periodontal Res 45:301-8. 2010
  9. pmc Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis
    Bianca Woehrl
    Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany
    J Clin Invest 121:3943-53. 2011
  10. doi Polymorphism of the complement 5 gene and cardiovascular outcome in patients with atherosclerosis
    Matthias Hoke
    Department of Internal Medicine II, Division of Angiology, Medical University Vienna, Vienna, Austria
    Eur J Clin Invest 42:921-6. 2012

Research Grants

  1. ANTIOXIDANTS AND FEMALE HORMONES IN THE ETIOLOGY OF RA
    Elizabeth Karlson; Fiscal Year: 2002
  2. Role of IL-8 in Cell Migration and Proliferation
    Ingrid Schraufstatter; Fiscal Year: 2004
  3. Activation and regulation of the lectin pathway
    Nenoo Rawal; Fiscal Year: 2007

Scientific Experts

Detail Information

Publications145 found, 100 shown here

  1. doi Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus
    E Y M G Fung
    Juvenile Diabetes Research Foundation Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    Genes Immun 10:188-91. 2009
    ..70 x 10(-3) to 3.20 x 10(-5). These findings extend our knowledge of susceptibility locus sharing across different autoimmune diseases, and provide convincing evidence that the RA/SLE locus 6q23/TNFAIP3 is a newly identified T1D locus...
  2. pmc TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study
    Robert M Plenge
    Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA, USA
    N Engl J Med 357:1199-209. 2007
    ..We carried out a genomewide association analysis to identify additional genetic loci associated with an increased risk of rheumatoid arthritis...
  3. pmc A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis
    Fina A S Kurreeman
    Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
    PLoS Med 4:e278. 2007
    ..Based on functional data in mice, we hypothesized that the immune-related genes complement component 5 (C5) and/or TNF receptor-associated factor 1 (TRAF1), located on Chromosome 9q33-34, would represent ..
  4. doi Association of the TRAF1-C5 locus on chromosome 9 with juvenile idiopathic arthritis
    Edward M Behrens
    The Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Arthritis Rheum 58:2206-7. 2008
  5. doi Association of the TRAF1/C5 locus with increased mortality, particularly from malignancy or sepsis, in patients with rheumatoid arthritis
    Vasileios F Panoulas
    Dudley Group of Hospitals National Health Service Trust, Dudley, UK
    Arthritis Rheum 60:39-46. 2009
    Recent genome-wide association studies have identified TRAF1/C5 as a rheumatoid arthritis (RA) susceptibility locus...
  6. pmc Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations
    Hye Soon Lee
    Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Seoul, South Korea
    Arthritis Rheum 60:364-71. 2009
    ..The aim of this study was to determine whether the genetic variants at 4q27, 6q23, CCL21, TRAF1/C5, and CD40 identified in Caucasians are also associated with RA in a Korean case-control collection...
  7. doi Susceptibility variants for rheumatoid arthritis in the TRAF1-C5 and 6q23 loci: a meta-analysis
    Nikolaos A Patsopoulos
    Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
    Ann Rheum Dis 69:561-6. 2010
    Genome-wide association studies have proposed susceptibility variants for rheumatoid arthritis in the TRAF1-C5 locus and 6q23 region...
  8. doi Single nucleotide polymorphisms of complement component 5 and periodontitis
    L Chai
    Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
    J Periodontal Res 45:301-8. 2010
    ..This study investigated whether tagging single nucleotide polymorphisms (SNPs) of the gene encoding complement component 5 (C5) are associated with periodontitis in a Hong Kong Chinese population.
  9. pmc Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis
    Bianca Woehrl
    Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany
    J Clin Invest 121:3943-53. 2011
    ..genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome...
  10. doi Polymorphism of the complement 5 gene and cardiovascular outcome in patients with atherosclerosis
    Matthias Hoke
    Department of Internal Medicine II, Division of Angiology, Medical University Vienna, Vienna, Austria
    Eur J Clin Invest 42:921-6. 2012
    ..Previously, we found a single-nucleotide polymorphism (SNP) in the complement 5 gene (C5 rs17611, A>G) independently associated with stroke...
  11. pmc Caveolin-1 and dynamin-2 are essential for removal of the complement C5b-9 complex via endocytosis
    Oren Moskovich
    Departments of Cell and Developmental Biology, Sackler School of Medicine, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    J Biol Chem 287:19904-15. 2012
    ..element of both innate and adaptive immunity, is executing complement-dependent cytotoxicity (CDC) with its C5b-9 protein complex that is assembled on cell surfaces and transmits to the cell death signals...
  12. pmc Assembly and regulation of the membrane attack complex based on structures of C5b6 and sC5b9
    Michael A Hadders
    Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
    Cell Rep 1:200-7. 2012
    ..Cleavage of C5 to C5b results in marked conformational changes, distinct from those observed in the homologous C3-to-C3b transition...
  13. ncbi An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice
    Jayakrishna Ambati
    Department of Ophthalmology, University of Kentucky, 740 South Limestone Street, Lexington, Kentucky 40536 0284, USA
    Nat Med 9:1390-7. 2003
    ..RPE or choroidal endothelial production of Ccl-2 induced by complement C5a and IgG may mediate choroidal macrophage infiltration into aged wild-type choroids...
  14. doi Replication of the tumor necrosis factor receptor-associated factor 1/complement component 5 region as a susceptibility locus for rheumatoid arthritis in a European family-based study
    F A S Kurreeman
    Leiden University Medical Center, Leiden, The Netherlands
    Arthritis Rheum 58:2670-4. 2008
    ..association study, that a 65-kb block encompassing tumor necrosis factor receptor-associated factor 1 (TRAF1) and C5 is strongly associated with rheumatoid arthritis (RA)...
  15. pmc Response gene to complement 32 is required for C5b-9 induced cell cycle activation in endothelial cells
    Matthew Fosbrink
    Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
    Exp Mol Pathol 86:87-94. 2009
    ..We previously showed that the C5b-9 assembly during complement activation induces cell cycle in human aortic EC (AEC) and SMC...
  16. doi Involvement of the c-jun N-terminal kinases JNK1 and JNK2 in complement-mediated cell death
    Dana Gancz
    Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Mol Immunol 47:310-7. 2009
    Cell death and survival signals activated by the complement membrane attack complex C5b-9 play important roles in complement-associated diseases and in antibody-based cancer therapy...
  17. pmc TRAF1/C5 polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies
    Jessica A B van Nies
    Department of Rheumatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Arthritis Res Ther 12:R38. 2010
    Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA)...
  18. pmc Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
    Darren Plant
    ARC Epidemiology Unit, Stopford Building, The University of Manchester, Manchester M13 9PT, UK
    Ann Rheum Dis 69:1548-53. 2010
    ..Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk...
  19. doi Cathepsin D is released after severe tissue trauma in vivo and is capable of generating C5a in vitro
    Markus Huber-Lang
    Department of Orthopedic Trauma, Hand, Plastic and Reconstructive Surgery, University Hospital Ulm, Germany
    Mol Immunol 50:60-5. 2012
    ..both the early activation of the complement cascade with an excessive generation of the potent anaphylatoxin C5a and the induction of apoptosis have been shown to modulate the post-traumatic immune response...
  20. pmc Crystal structure of C5b-6 suggests structural basis for priming assembly of the membrane attack complex
    Alexander E Aleshin
    Program on Infectious Diseases, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
    J Biol Chem 287:19642-52. 2012
    ..The first step in MAC assembly is cleavage of C5 to generate metastable C5b, which forms a stable complex with C6, termed C5b-6...
  21. pmc Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression
    Leticia Corrales
    Division of Oncology, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
    J Immunol 189:4674-83. 2012
    ..We focused our study on the production and role of the anaphylatoxin C5a, a potent immune mediator generated after complement activation...
  22. doi C5 complement deficiency in a Saudi family, molecular characterization of mutation and literature review
    Rand Arnaout
    King Faisal Specialist Hospital and Research Center, PO Box 3354, MBC 46, Riyadh, 11211, Kingdom of Saudi Arabia
    J Clin Immunol 33:871-5. 2013
    ..Only a small number of molecular studies have been carried out for the characterization of the underlying genetic defects in these cases...
  23. doi C3a, C5a renal expression and their receptors are correlated to severity of IgA nephropathy
    Lu Liu
    Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou University Institute of Nephrology, Zhengzhou, 450052, China
    J Clin Immunol 34:224-32. 2014
    ..Complement activation products C3a and C5a have broad pro-inflammatory potential through their receptors, C3aR and C5aR, and contribute to the pathogenesis of ..
  24. pmc Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta
    M Banadakoppa
    Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA
    Clin Exp Immunol 177:743-9. 2014
    ..Systemic levels of complement factors C3a and C5a were measured by enzyme-linked immunosorbent assay (ELISA)...
  25. doi Complement C5a potentiates uric acid crystal-induced IL-1β production
    Ling Ling An
    Department of Respiratory, Inflammation and Autoimmune Diseases, MedImmune, LLC, Gaithersburg, MD, USA
    Eur J Immunol 44:3669-79. 2014
    Anaphylatoxin C5a released upon complement activation is associated with both acute and chronic inflammations such as gout...
  26. doi TRAF1/C5 rs10818488 polymorphism is not a genetic risk factor for acquired aplastic anemia in a Chinese population
    Meili Ge
    State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China
    Hum Immunol 76:19-21. 2015
    The tumor necrosis factor receptor-associated factor 1/complement C5 (TRAF1/C5) genes have been suggested as two candidate genes for conferring susceptibility to autoimmunity and inflammation...
  27. pmc Functional analysis of a complement polymorphism (rs17611) associated with rheumatoid arthritis
    Joanna L Giles
    Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom
    J Immunol 194:3029-34. 2015
    ..Plasma levels of C5, C5a, and terminal complement complex were measured in healthy and RA donors and correlated to rs17611 polymorphic ..
  28. doi Increased expression of perforin, granzyme B, and C5b-9 in villitis of unknown etiology
    Y Ito
    Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3 25 8, Nishi Shinbashi, Minato ku, Tokyo 105 8461, Japan Department of Pathology, National Center for Child Health and Development, 2 10 1, Okura, Setagaya Ku, Tokyo 157 8535, Japan Department of Maternal Fetal Biology, National Research Institute for Child Health and Development, 2 10 1, Okura, Setagaya Ku, Tokyo 157 8535, Japan
    Placenta 36:531-7. 2015
    ..We aimed to verify whether apoptosis-related factors are increased in VUE placentas. Furthermore, we determined apoptosis of villous cells...
  29. pmc Exposure to the complement C5b-9 complex sensitizes 661W photoreceptor cells to both apoptosis and necroptosis
    Hui Shi
    Department of Cell Biology, UCL Institute of Ophthalmology, 11 43 Bath Street, London, EC1V 9EL, UK
    Apoptosis 20:433-43. 2015
    ..Here we have used the 661W cone photoreceptor cell line to ask whether exposure to the terminal complement complex C5b-9 induces cell death and/or modulates the sensitivity of these cells to other cellular stressors...
  30. doi Complement C5 Gene Confers Risk for Acute Anterior Uveitis
    Dengfeng Xu
    The First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People s Republic of China
    Invest Ophthalmol Vis Sci 56:4954-60. 2015
    Polymorphisms in the genes encoding C3 and C5 are associated with several immune-mediated diseases...
  31. pmc Copy number variations and gene polymorphisms of complement components in ocular Behcet's disease and Vogt-Koyanagi-Harada syndrome
    Dengfeng Xu
    The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P R China
    Sci Rep 5:12989. 2015
    ..The frequencies of having more than two copies of C3 were significantly increased in BD and VKH, whereas CNV of C5 was only associated with BD...
  32. ncbi Heteronuclear three-dimensional NMR spectroscopy of the inflammatory protein C5a
    E R Zuiderweg
    Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064
    Biochemistry 28:2387-91. 1989
    ..heteronuclear NMR spectroscopy for the assignment of 1H and 15N resonances of the inflammatory protein C5a (MW 8500), uniformly labeled with 15N, is demonstrated at a protein concentration of 0.7 mM...
  33. ncbi Molecular analysis of human complement component C5: localization of the structural gene to chromosome 9
    R A Wetsel
    Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037
    Biochemistry 27:1474-82. 1988
    A human C5 clone (pC5HG2) was isolated from a cDNA library constructed from Hep G2 mRNA...
  34. ncbi Site-specific disulfide capture of agonist and antagonist peptides on the C5a receptor
    Elizabeth Buck
    Sunesis Pharmaceuticals Inc, South San Francisco, California 94080, USA
    J Biol Chem 280:4009-12. 2005
    ..One of the better characterized peptidic ligands is the chemotactic cytokine complement factor 5a (C5a), a 74-amino acid helical bundle...
  35. pmc Investigating the viability of genetic screening/testing for RA susceptibility using combinations of five confirmed risk loci
    Annie McClure
    ARC Epidemiology Unit, Stopford Building, The University of Manchester, Manchester, UK
    Rheumatology (Oxford) 48:1369-74. 2009
    ..shared epitope (SE) of HLA--DRB1, the PTPN22 gene, a locus on 6q23, the STAT4 gene and a locus mapping to the TRAF1/C5 genetic region--have now been unequivocally confirmed as conferring susceptibility to RA...
  36. pmc The complement component 5 gene and age-related macular degeneration
    Dominique C Baas
    Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences KNAW, Amsterdam, The Netherlands
    Ophthalmology 117:500-11. 2010
    To investigate the association between variants in the complement component 5 (C5) gene and age-related macular degeneration (AMD).
  37. doi Correlation of plasma complement split product levels with allergic respiratory disease activity and relation to allergen immunotherapy
    Corinna Bowser
    Department of Medicine, State University of New York SUNY Downstate Medical Center, Brooklyn, New York 11203, USA
    Ann Allergy Asthma Immunol 104:42-9. 2010
    ..dust mite and grass pollen, and mast cell tryptase are known to generate the complement split products (CSPs) C5a and C3a, which can then trigger allergic inflammation...
  38. pmc Cumulative association of 22 genetic variants with seropositive rheumatoid arthritis risk
    Elizabeth W Karlson
    75 Francis Street, Boston, MA 02115, USA
    Ann Rheum Dis 69:1077-85. 2010
    ..This study examined whether a cumulative score based on 22 validated genetic risk alleles for seropositive RA would identify high-risk, asymptomatic individuals who might benefit from preventive interventions...
  39. pmc Genetic risk factors in lupus nephritis and IgA nephropathy--no support of an overlap
    Mai Tuyet Vuong
    Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
    PLoS ONE 5:e10559. 2010
    ..In several autoimmune diseases, particularly in SLE, IRF5, STAT4 genes and TRAF1-C5 locus have been shown to be important candidate genes...
  40. doi Effects of C5 complement inhibitor pexelizumab on outcome in high-risk coronary artery bypass grafting: combined results from the PRIMO-CABG I and II trials
    Peter K Smith
    Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, NC 27710, USA
    J Thorac Cardiovasc Surg 142:89-98. 2011
    ..of Infarction and Mortality in Coronary Artery Bypass Graft Surgery I (PRIMO-CABG I) trial (n = 3099) indicated that C5 complement inhibition with pexelizumab might reduce myocardial infarction (MI) and postoperative mortality...
  41. pmc Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex
    Nick S Laursen
    Department of Molecular Biology, Aarhus University, Aarhus, Denmark
    EMBO J 30:606-16. 2011
    ..immune system, and its activation initiates a strong inflammatory response and cleavage of the proteins C3 and C5 by proteolytic enzymes, the convertases...
  42. pmc Early complementopathy after multiple injuries in humans
    Anne Maud Burk
    Department of Traumatology, Hand, Plastic, and Reconstructive Surgery, University Hospital Ulm, Ulm, Germany
    Shock 37:348-54. 2012
    ..Serum levels of the complement activation products C3a and C5a were significantly elevated throughout the entire observation period and correlated with the severity of traumatic ..
  43. doi Complement factor C5a as mast cell activator mediates vascular remodelling in vein graft disease
    Margreet R De Vries
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden, The Netherlands
    Cardiovasc Res 97:311-20. 2013
    ..Interestingly, mast cells can be activated by complement factor C5a and, therefore, a direct role for C5a-mediated mast cell activation in vein graft disease is anticipated...
  44. ncbi Complement factors in newly diagnosed Nigerian schizoprenic patients and those on antipsychotic therapy
    O B Idonije
    1Department of Chemical Pathology and Immunology, University of Ibadan, Ibadan, Oyo State
    Niger J Physiol Sci 27:19-21. 2012
    ..this issue, levels of Complement regulators (C1 inhibitor and C3 activator) and complement factors (C1q, C3c, C4 and C5) were determined in the serum of newly diagnosed drug free schizophrenic patients, schizophrenic patients on ..
  45. pmc Complement polymorphisms and cognitive dysfunction after carotid endarterectomy
    Eric J Heyer
    Department of Anesthesiology, Columbia University, New York, New York, USA
    J Neurosurg 119:648-54. 2013
    ..There are single nucleotide polymorphisms (SNPs) that predispose patients to postoperative cognitive dysfunction (CD). We aim to assess the predictability of three complement cascade-related SNPs for CD in patients having CEAs...
  46. doi Human skin mast cells express complement factors C3 and C5
    Yoshihiro Fukuoka
    Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
    J Immunol 191:1827-34. 2013
    We examine whether complement factor C3 or C5 is synthesized by human skin-derived mast cells and whether their synthesis is regulated by cytokines...
  47. doi Genetic variants in C5 and poor response to eculizumab
    Jun ichi Nishimura
    From Osaka University Graduate School of Medicine J N, M Y, H S, Y K and World Premier International Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka University, Suita T K, Medical Research Institute and Hard Tissue Genome Research Center, Tokyo Medical and Dental University S H, J I, Tokyo Medical University K O, and Alexion Pharma M H, Tokyo, Tokai University School of Medicine, Isehara K A, Fukushima Medical University, Fukushima H N, T S, Ichinomiya Municipal Hospital, Ichinomiya K K, Hamanomachi Hospital, Fukuoka T E, Yamaguchi Grand Medical Center, Hofu T T, Niigata University Medical and Dental Hospital, Niigata M M, Japanese Red Cross Takayama Hospital, Takayama T M, and Iwate Prefectual Central Hospital, Morioka Y W all in Japan University of Buenos Aires, Buenos Aires A L B, A L and Alexion Pharmaceuticals, Cheshire, CT L L, K J, Department of Biochemistry
    N Engl J Med 370:632-9. 2014
    Eculizumab is a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement-mediated hemolysis associated with paroxysmal nocturnal hemoglobinuria (PNH)...
  48. pmc Cholesterol crystals induce complement-dependent inflammasome activation and cytokine release
    Eivind O Samstad
    Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim N 7491, Norway
    J Immunol 192:2837-45. 2014
    ..CC employed C5a in the release of a number of cytokines in whole blood, including IL-1β and TNF...
  49. doi C5a stimulates the proliferation of breast cancer cells via Akt-dependent RGC-32 gene activation
    Yi Lu
    Department of General Surgery, Suzhou Kowloon Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Suzhou, Jiangsu 215021, P R China
    Oncol Rep 32:2817-23. 2014
    ..We focused our study on the potential roles of the anaphylatoxins C3a and C5a in the proliferation of human breast cancer, as two important immune mediators generated after complement ..
  50. pmc C5a and toll-like receptor 4 crosstalk in retinal pigment epithelial cells
    Yi Zhu
    The People s Hospital of Kai County, Chongqing, China
    Mol Vis 21:1122-9. 2015
    To investigate the effect of the complement activation product C5a on toll-like receptor (TLR) 4-induced responses in RPE cells.
  51. pmc Association of Complement C5 Gene Polymorphisms with Proliferative Diabetic Retinopathy of Type 2 Diabetes in a Chinese Han Population
    Dengfeng Xu
    Chongqing General Hospital, Chongqing EYE and ENT Hospital, Chongqing, P R China
    PLoS ONE 11:e0149704. 2016
    To investigate the association of C5 SNPs with proliferative diabetic retinopathy (PDR) of type 2 diabetes (T2D).
  52. ncbi Formation of high affinity C5 convertase of the classical pathway of complement
    Nenoo Rawal
    Department of Biochemistry, University of Texas Health Science Center, Tyler, Texas 75703, USA
    J Biol Chem 278:38476-83. 2003
    C3/C5 convertase is a serine protease that cleaves C3 and C5. In the present study we examined the C5 cleaving properties of classical pathway C3/C5 convertase either bound to the surface of sheep erythrocytes or in its free soluble form...
  53. ncbi Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humans
    Sonja Hillebrandt
    Department of Medicine III, University Hospital Aachen, Aachen University, Aachen, Germany
    Nat Genet 37:835-43. 2005
    ..Small molecule inhibitors of the C5a receptor had antifibrotic effects in vivo, and common haplotype-tagging polymorphisms of the human gene C5 were ..
  54. ncbi Identification of complement activation sites in human immunodeficiency virus type-1 glycoprotein gp120
    C Susal
    Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Germany
    Blood 87:2329-36. 1996
    ..In the current study, the complement proteins C4,C3,C5,C9, and properdin were found to bind to a synthetic peptide covering positions 233-251 of the gp120BRU sequence on ..
  55. ncbi C3a and C5a are chemotaxins for human mast cells and act through distinct receptors via a pertussis toxin-sensitive signal transduction pathway
    G Nilsson
    Department of Pathology, University Hospital, University of Uppsala, Sweden
    J Immunol 157:1693-8. 1996
    ..Since most natural leukocyte secretagogues also induce cell migration, and since the anaphylatoxins C3a and C5a are mast cell secretagogues, we hypothesized that both C3a and C5a are also mast cell chemotaxins...
  56. ncbi rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues
    L Ottonello
    Department of Internal Medicine, University of Genova, Italy
    J Immunol 162:6510-7. 1999
    Human C5a is a potent chemoattractant for granulocytes, monocytes, and dendritic cells. In mice C5a has been shown to be chemotactic for germinal center (GC) B cells...
  57. doi Fibrotic mechanisms in idiopathic rapidly progressive glomerulonephritis: the role of TGF-beta1 and C5b-9
    Lazaros Gionanlis
    Department of Nephrology, G Papanikolaou General Hospital, Thessaloniki, Greece
    Ren Fail 30:239-46. 2008
    ..Idiopathic IRPGN is a form of renal vasculitis in which a high chronicity index is present despite minimal impairment of renal function. The present study investigated the mechanisms underlining the relatively early appearance of fibrosis...
  58. doi C3a and C5a are chemotactic factors for human mesenchymal stem cells, which cause prolonged ERK1/2 phosphorylation
    Ingrid U Schraufstatter
    Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA
    J Immunol 182:3827-36. 2009
    ..activation occurs whenever there is tissue damage, the effects of the complement activation products C3a and C5a on MSCs were examined...
  59. doi Skipping of exon 30 in C5 gene results in complete human C5 deficiency and demonstrates the importance of C5d and CUB domains for stability
    P Aguilar-Ramirez
    Departamento de Imunologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Brazil
    Mol Immunol 46:2116-23. 2009
    The deficiency of complement C5 is rare and frequently associated with severe and recurrent infections, especially caused by Neisseria spp...
  60. pmc Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus
    Nick S Laursen
    Department of Molecular Biology, University of Aarhus, DK 8000 Aarhus, Denmark
    Proc Natl Acad Sci U S A 107:3681-6. 2010
    Staphylococcus aureus secretes the SSL7 protein as part of its immune evasion strategy. The protein binds both complement C5 and IgA, yet it is unclear whether SSL7 cross-links these two proteins and, if so, what purpose this serves the ..
  61. doi Thrombin generates previously unidentified C5 products that support the terminal complement activation pathway
    Michael J Krisinger
    Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
    Blood 120:1717-25. 2012
    ..of thrombin and C5 convertase on C5 in purified and plasma-based systems, measuring release of the anaphylatoxin C5a, and generation of C5b, the initial component of the lytic membrane attack complex...
  62. pmc Plasma clearance of the human C5a anaphylatoxin by binding to leucocyte C5a receptors
    M Oppermann
    Department of Immunology, University of Gottingen, Germany
    Immunology 82:516-21. 1994
    The C5a anaphylatoxin is a potent complement-derived mediator of inflammation with chemotactic activity...
  63. ncbi The complement component C5a induces the expression of plasminogen activator inhibitor-1 in human macrophages via NF-kappaB activation
    S P Kastl
    Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
    J Thromb Haemost 4:1790-7. 2006
    ..Complement components were identified in atherosclerotic plaques, and a correlation between adverse events and C5a plasma levels was found...
  64. doi Regulation of IL-8 production by complement-activated product, C5a, in vitro and in vivo during sepsis
    Liyan Wang
    Department of Molecular Immunology, Institute of Basic Medical Sciences, Taiping Road, No 27, Beijing 100850, People s Republic of China
    Clin Immunol 137:157-65. 2010
    Excessive complement-activated product complement 5a (C5a) has been implicated in the pathogenesis of sepsis development...
  65. ncbi Lack of association of PTPN22, STAT4 and TRAF1/C5 gene polymorphisms with cardiovascular risk in rheumatoid arthritis
    R Palomino-Morales
    Instituto de Parasitologia y Biomedicina Lopez Neyra, Consejo Superior de Investigaciones Cientificas CSIC, Granada, Spain
    Clin Exp Rheumatol 28:695-701. 2010
    To determine whether the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction or increased ..
  66. doi Association of complement 5 genetic polymorphism with renal allograft outcomes in Korea
    Jong Cheol Jeong
    Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
    Nephrol Dial Transplant 26:3378-85. 2011
    ..Complement 5 (C5) is a pivotal complement, which initiates the assembly of the membrane attack complex, and mediates chemotaxis of ..
  67. doi Human colonic epithelial cells detect and respond to C5a via apically expressed C5aR through the ERK pathway
    Qi Cao
    Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
    Am J Physiol Cell Physiol 302:C1731-40. 2012
    ..The split component C5a is a potent proinflammatory molecule, and the C5a receptor (C5aR) CD88 has been reported on multiple cell types...
  68. ncbi Structure, function and control of complement C5 and its proteolytic fragments
    N S Laursen
    Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, DK 8000 Aarhus, Denmark
    Curr Mol Med 12:1083-97. 2012
    ..elicits proteolytic cascades which eventually results in the cleavage of the C5 protein into two fragments, C5a and C5b. The small anaphylatoxin C5a induces a variety of biological responses upon binding to the 7TM receptors C5aR and ..
  69. doi Associations between TNFSF4 and TRAF1-C5 gene polymorphisms and systemic lupus erythematosus: a meta-analysis
    Young Ho Lee
    Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, 126 1 Seoul, Republic of Korea
    Hum Immunol 73:1050-4. 2012
    The aim of this study was to determine whether tumor necrosis factor superfamily 4 (TNFSF4) and TNF receptor-associated factor 1-complement 5 (TRAF1-C5) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE).
  70. ncbi Fifth component of human complement: purification from plasma and polypeptide chain structure
    B F Tack
    Biochemistry 18:1490-7. 1979
  71. ncbi Complete cDNA sequence of human complement pro-C5. Evidence of truncated transcripts derived from a single copy gene
    D L Haviland
    Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110
    J Immunol 146:362-8. 1991
    Two truncated human C5 clones, pHC5A and pHC5B, were isolated from an adult human liver cDNA library, and contained inserts of 2930 and 2181 bp, respectively...
  72. ncbi Tertiary structure of human complement component C5a in solution from nuclear magnetic resonance data
    E R Zuiderweg
    Research NMR Group, Abbott Laboratories, Abbott Park, Illinois 60064
    Biochemistry 28:172-85. 1989
    The tertiary structure for the region 1-63 of the 74 amino acid human complement protein C5a in solution was calculated from a large number of distance constraints derived from nuclear Overhauser effects with an angular distance geometry ..
  73. ncbi Complete primary structure and functional characterization of the sixth component of the human complement system. Identification of the C5b-binding domain in complement C6
    J A Haefliger
    Institute of Biochemistry, University of Lausanne, Switzerland
    J Biol Chem 264:18041-51. 1989
    ..is one of five plasma proteins that are incorporated into the lytic terminal complement complex on lipid membranes (C5b-9m) upon activation of the complement cascade...
  74. ncbi Molecular organization and function of the complement system
    H J Muller-Eberhard
    Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037
    Annu Rev Biochem 57:321-47. 1988
  75. ncbi Sequence-specific assignments in the 1H NMR spectrum of the human inflammatory protein C5a
    E R Zuiderweg
    Pharmaceutical Discovery, Abbott Laboratories, Abbott Park, Illinois 60064
    Biochemistry 27:3568-80. 1988
    Full sequence-specific assignments for the 1H NMR lines of the backbone protons of the human complement factor C5a are described and documented. The results were obtained by largely following the methodology developed by Wüthrich et al...
  76. ncbi Evidence that C5b recognizes and mediates C8 incorporation into the cytolytic complex of complement
    J L Stewart
    J Immunol 139:1960-4. 1987
    The aim of this study was to identify constituents of the intermediate C5b-7 complex of human complement that mediate binding of C8 and formation of C5b-8...
  77. ncbi Mitogen-activated protein kinase activation requires two signal inputs from the human anaphylatoxin C5a receptor
    A M Buhl
    Department of Chemistry, Aarhus University, Denmark
    J Biol Chem 270:19828-32. 1995
    The anaphylatoxin C5a receptor activates the Ras/Raf/mitogen-activated protein (MAP) kinase pathway in human neutrophils...
  78. ncbi [Chemico-enzymatic synthesis, cloning and expression of a gene for an analog of human anaphylatoxin C5a]
    I N Babkina
    Bioorg Khim 21:359-64. 1995
    Chemical-enzymatic synthesis and cloning of a gene for a human anaphylatoxin C5a analog were carried out. Recombinant plasmid pRC5a providing the expression of the synthetic gene in the Escherichia coli cells was obtained...
  79. ncbi Inherited human complement C5 deficiency. Nonsense mutations in exons 1 (Gln1 to Stop) and 36 (Arg1458 to Stop) and compound heterozygosity in three African-American families
    X Wang
    Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 154:5464-71. 1995
    ..population, the exons and intron/exon boundaries of the C5 structural genes from three C5-deficient (C5D) African-American families were sequenced, revealing two nonsense mutations...
  80. ncbi Complement activation by recombinant HIV-1 glycoprotein gp120
    C Susal
    Department of Transplantation Immunology, University of Heidelberg, Germany
    J Immunol 152:6028-34. 1994
    ..We found that the complement proteins C4, C3d, C5b-9, and properdin bind to rgp 120-coated CD4+ T cells of healthy individuals when incubated in autologous serum...
  81. ncbi In Xenopus oocytes the human C3a and C5a receptors elicit a promiscuous response to the anaphylatoxins
    R S Ames
    Department of Molecular Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa 19406 0939, USA
    FEBS Lett 395:157-9. 1996
    ..Conversely, oocytes co-injected with the C5a receptor and total RNA isolated from U937 cells responded to C5a as well as to C3a and the C3a synthetic peptide...
  82. pmc Solution structure of a unique C5a semi-synthetic antagonist: implications in receptor binding
    X Zhang
    CIBA GEIGY Corporation, Pharmaceuticals Division, Summit, New Jersey 07901, USA
    Protein Sci 6:65-72. 1997
    The tertiary structure of a unique C5a receptor antagonist was determined by two-dimensional NMR spectroscopy. The core domain of this 8-kDa antagonist exists as an antiparallel helical bundle, similar to recombinant human (rh)-C5a...
  83. ncbi TNF-alpha-mediated expression of the receptor for anaphylatoxin C5a on neurons in experimental Listeria meningoencephalitis
    P F Stahel
    Department of Microbiology, University of Alabama, Birmingham 35294, USA
    J Immunol 159:861-9. 1997
    The anaphylatoxin C5a has been implicated in the pathogenesis of bacterial meningitis as a potent mediator of inflammation in the subarachnoid space...
  84. ncbi Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils
    N T Luu
    Department of Physiology, The Medical School, University of Birmingham, Birmingham, United Kingdom
    J Immunol 164:5961-9. 2000
    ..If fMLP, IL-8, zymosan-activated plasma (a source of activated complement factor C5a), epithelial cell-derived neutrophil-activating peptide (ENA-78), or growth-regulating oncogene, GRO-alpha, was ..
  85. ncbi Complement C3b interactions studied with surface plasmon resonance technique
    T S Jokiranta
    Department of Microbiology and Infectious Diseases, Flinders Medical Centre, SA 5042 Bedford Park, Australia
    Int Immunopharmacol 1:495-506. 2001
    ..amine C3b coupling, we analyzed and compared the binding of four C3b ligands to the surface: factor B, factor H, C5 and the soluble complement receptor 1 (sCR1, CD35)...
  86. pmc C5a anaphylatoxin is a major regulator of activating versus inhibitory FcgammaRs in immune complex-induced lung disease
    Nelli Shushakova
    Department of Clinical Immunology, Medical School Hannover, Hannover, Germany
    J Clin Invest 110:1823-30. 2002
    IgG Fc receptors (FcgammaRs, especially FcgammaRIII) and complement (in particular, C5a anaphylatoxin) are critical effectors of the acute inflammatory response to immune complexes (ICs)...
  87. ncbi Expression and characterization of the C345C/NTR domains of complement components C3 and C5
    Chuong Thu Thai
    Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA
    J Immunol 171:6565-73. 2003
    Complement components C3, C4, and C5 are members of the thioester-containing alpha-macroglobulin protein superfamily...
  88. ncbi Variations in the C3, C3a receptor, and C5 genes affect susceptibility to bronchial asthma
    Koichi Hasegawa
    Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research RIKEN, Yokohama, Japan
    Hum Genet 115:295-301. 2004
    ..to BA, we screened single nucleotide polymorphisms (SNPs) in C3, C5, the C3a receptor gene (C3AR1), and the C5a receptor gene (C5R1) and performed association studies in the Japanese population...
  89. ncbi C5 complement deficiency in a Spanish family. Molecular characterization of the double mutation responsible for the defect
    Eva Delgado-Cerviño
    Unit of Immunology, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain
    Mol Immunol 42:105-11. 2005
    The complement C5 deficiency is a recessive autosomal defect associated with recurrent infectious episodes, generally caused by Gram-negative micro-organisms...
  90. ncbi Complement C5a is a key mediator of meconium-induced neutrophil activation
    Albert Castellheim
    Department of Pediatric Research, Rikshospitalet University Hospital, 0027 Oslo, Norway
    Pediatr Res 57:242-7. 2005
    ..Complement was inhibited using the MAb 166-32 and 137-26, which block factor D and neutralize C5a, respectively...
  91. ncbi Functional insights from the structure of the multifunctional C345C domain of C5 of complement
    Janice Bramham
    Schools of Chemistry and Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, Scotland, UK
    J Biol Chem 280:10636-45. 2005
    ..It interacts with enzymes that convert C5 to C5b, the first step in the assembly of the membrane attack complex; it also binds to the membrane attack complex ..
  92. ncbi Essential role for the second extracellular loop in C5a receptor activation
    Jeffery M Klco
    Department of Medicine, Washington University School of Medicine, Campus Box 8127, 660 S Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Struct Mol Biol 12:320-6. 2005
    ..These results demonstrate an unexpected role for EC2 as a negative regulator of C5a receptor activation...
  93. ncbi Recombinant C345C and factor I modules of complement components C5 and C7 inhibit C7 incorporation into the complement membrane attack complex
    Chuong Thu Thai
    Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA
    J Immunol 174:6227-32. 2005
    ..Using this method, we found that C7 binds to surface-bound C5b,6 with a K(d) of approximately 3 pM, and that micromolar concentrations of either rC5-C345C or rC7-FIMs inhibit ..
  94. pmc Drusen complement components C3a and C5a promote choroidal neovascularization
    Miho Nozaki
    Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40536, USA
    Proc Natl Acad Sci U S A 103:2328-33. 2006
    ..Here we provide evidence that bioactive fragments of these complement components (C3a and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce VEGF expression in vitro and in vivo...
  95. ncbi C5b-9-induced endothelial cell proliferation and migration are dependent on Akt inactivation of forkhead transcription factor FOXO1
    Matthew Fosbrink
    Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 281:19009-18. 2006
    ..Activation of complement and assembly of the C5b-9 complement complex have been implicated in the pre-lesional stage of atherogenesis and progression of the ..

Research Grants3

  1. ANTIOXIDANTS AND FEMALE HORMONES IN THE ETIOLOGY OF RA
    Elizabeth Karlson; Fiscal Year: 2002
    ..RA will be confirmed by a screening questionnaire regarding rheumatic symptoms and review of medical records. The study will identify potentially modifiable risk factors for primary prevention of RA. ..
  2. Role of IL-8 in Cell Migration and Proliferation
    Ingrid Schraufstatter; Fiscal Year: 2004
    ....
  3. Activation and regulation of the lectin pathway
    Nenoo Rawal; Fiscal Year: 2007
    ..However, our own studies of the lectin pathway suggest that the formation, activity, and regulation of C3/C5 convertases on an activator differ significantly from those of the classical pathway...