complement membrane attack complex

Summary

Summary: A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.

Top Publications

  1. ncbi CD59 efficiently protects human NT2-N neurons against complement-mediated damage
    E D Pedersen
    Institute of Immunology, Rikshospitalet HF, University of Oslo, Oslo, Norway
    Scand J Immunol 66:345-51. 2007
  2. doi Complement-associated deposits in the human retina
    Aditya Seth
    Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada
    Invest Ophthalmol Vis Sci 49:743-50. 2008
  3. ncbi A common fold mediates vertebrate defense and bacterial attack
    Carlos J Rosado
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
    Science 317:1548-51. 2007
  4. ncbi Early complement activation and decreased levels of glycosylphosphatidylinositol-anchored complement inhibitors in human and experimental diabetic retinopathy
    Jing Zhang
    Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA
    Diabetes 51:3499-504. 2002
  5. doi The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative pathway amplification
    Morten Harboe
    Institute of Immunology, University of Oslo and Rikshospitalet University Hospital, NO 0027 Oslo, Norway
    Mol Immunol 47:373-80. 2009
  6. pmc Relationship between complement membrane attack complex, chemokine (C-C motif) ligand 2 (CCL2) and vascular endothelial growth factor in mouse model of laser-induced choroidal neovascularization
    Juan Liu
    Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock, Arizona 72205, USA
    J Biol Chem 286:20991-1001. 2011
  7. pmc The tick salivary protein Salp15 inhibits the killing of serum-sensitive Borrelia burgdorferi sensu lato isolates
    Tim J Schuijt
    Leiden University Medical Centre, Department of Medical Microbiology, University of Leiden, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Infect Immun 76:2888-94. 2008
  8. ncbi Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration
    Zhi Qi Xiong
    Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Neurosci 23:955-60. 2003
  9. pmc The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury
    Constantino Fondevila
    Dumont University of California at Los Angeles Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095, USA
    Liver Transpl 14:1133-41. 2008
  10. pmc PRELP protein inhibits the formation of the complement membrane attack complex
    Kaisa E Happonen
    Department of Laboratory Medicine, Division of Medical Protein Chemistry, Wallenberg Laboratory, Skane University Hospital, Lund University, S 20502 Lund, Sweden
    J Biol Chem 287:8092-100. 2012

Detail Information

Publications196 found, 100 shown here

  1. ncbi CD59 efficiently protects human NT2-N neurons against complement-mediated damage
    E D Pedersen
    Institute of Immunology, Rikshospitalet HF, University of Oslo, Oslo, Norway
    Scand J Immunol 66:345-51. 2007
    ..In conclusion, CD59 is essential for protecting human NT2-N neurons against complement-mediated damage, which is known to occur in a number of clinical conditions including stroke...
  2. doi Complement-associated deposits in the human retina
    Aditya Seth
    Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada
    Invest Ophthalmol Vis Sci 49:743-50. 2008
    ..The purpose of this study was to investigate complement activation and associated inflammatory mechanisms in normal, aged human retina...
  3. ncbi A common fold mediates vertebrate defense and bacterial attack
    Carlos J Rosado
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
    Science 317:1548-51. 2007
    ..Sequence similarity between bacterial and vertebrate MACPF domains suggests that the fold of the CDCs, a family of proteins important for bacterial pathogenesis, is probably used by vertebrates for defense against infection...
  4. ncbi Early complement activation and decreased levels of glycosylphosphatidylinositol-anchored complement inhibitors in human and experimental diabetic retinopathy
    Jing Zhang
    Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA
    Diabetes 51:3499-504. 2002
    ..These are novel clues for probing how diabetes affects and damages vascular cells...
  5. doi The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative pathway amplification
    Morten Harboe
    Institute of Immunology, University of Oslo and Rikshospitalet University Hospital, NO 0027 Oslo, Norway
    Mol Immunol 47:373-80. 2009
    ..In conclusion, the down-stream effect of LP activation depends strongly on AP amplification in normal human serum and in the C2 bypass pathway...
  6. pmc Relationship between complement membrane attack complex, chemokine (C-C motif) ligand 2 (CCL2) and vascular endothelial growth factor in mouse model of laser-induced choroidal neovascularization
    Juan Liu
    Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock, Arizona 72205, USA
    J Biol Chem 286:20991-1001. 2011
    The present study investigated the interactions among the complement membrane attack complex (MAC), CCL2, and VEGF that occur in vivo during the development of choroidal neovascularization (CNV)...
  7. pmc The tick salivary protein Salp15 inhibits the killing of serum-sensitive Borrelia burgdorferi sensu lato isolates
    Tim J Schuijt
    Leiden University Medical Centre, Department of Medical Microbiology, University of Leiden, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Infect Immun 76:2888-94. 2008
    ..In the presence of normal human serum, serum-sensitive Borrelia burgdorferi requires protection against complement-mediated killing, which is provided, at least in part, by the binding to the tick salivary protein Salp15...
  8. ncbi Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration
    Zhi Qi Xiong
    Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Neurosci 23:955-60. 2003
    ..Deposition of the complement MAC in cortical gray matter may contribute to epileptic seizures and cell death in diverse diseases of the human brain...
  9. pmc The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury
    Constantino Fondevila
    Dumont University of California at Los Angeles Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095, USA
    Liver Transpl 14:1133-41. 2008
    ..This is the first report using a clinically relevant liver cold ischemia model to show that local MAC inhibition attenuates IRI cascade in OLT recipients...
  10. pmc PRELP protein inhibits the formation of the complement membrane attack complex
    Kaisa E Happonen
    Department of Laboratory Medicine, Division of Medical Protein Chemistry, Wallenberg Laboratory, Skane University Hospital, Lund University, S 20502 Lund, Sweden
    J Biol Chem 287:8092-100. 2012
    ..The net outcome of PRELP-mediated complement inhibition will highly depend on the local concentration of other complement modulating molecules as well as on the local concentration of available complement proteins...
  11. ncbi Level of complement activity predicts cardiac dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention
    Sune Haahr-Pedersen
    Department of Cardiology P, Gentofte University Hospital, Niels Andersens Vej 65, Copenhagen, Denmark
    J Invasive Cardiol 21:13-9. 2009
    ..We evaluated the potential association between MBL and sC5b-9 in plasma and subsequent cardiac dysfunction in patients with STEMI treated with primary percutaneous coronary intervention (pPCI)...
  12. pmc Endotoxin-induced lung inflammation is independent of the complement membrane attack complex
    R B Brauer
    Department of Surgery, Immunology and Hygiene, Klinikum rechts der Isar, Technische Universitat Munchen, D 81675 Munich, Germany
    Infect Immun 68:1626-32. 2000
    ....
  13. ncbi Necrotizing myopathy with microvascular deposition of the complement membrane attack complex
    J De Bleecker
    Department of Neurology, Ghent University Hospital, Ghent, Belgium
    Clin Neuropathol 23:76-9. 2004
    ..The link between the muscle fiber necrosis and the microangiopathy is unclear. Absence of prominent inflammatory changes in a diagnostic muscle biopsy does not exclude the diagnosis of a treatable autoimmune inflammatory myopathy...
  14. pmc Time course of complement activation and inhibitor expression after ischemic injury of rat myocardium
    A Vakeva
    Department of Bacteriology and Immunology, University of Helsinki, Finland
    Am J Pathol 144:1357-68. 1994
    ..Deposition of C1 and late C components also starts during the early hours (2 to 4 hours) after ischemia. Subsequent loss of the protective CD59 antigen may initiate postinjury clearance of the irreversibly damaged tissue...
  15. doi Complement activation, endothelial dysfunction, insulin resistance and chronic heart failure
    Mette Bjerre
    Medical Research Laboratories, Clinical Institute and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark
    Scand Cardiovasc J 44:260-6. 2010
    ....
  16. ncbi The terminal complement complex inhibits apoptosis in vascular smooth muscle cells by activating an autocrine IGF-1 loop
    Thomas P Zwaka
    Department of Internal Medicine II, University of Ulm, Germany
    FASEB J 17:1346-8. 2003
    ..We conclude that C5b-9 inhibits apoptosis in SMCs by inducing an autocrine IGF-1 loop. This mechanism may contribute to the accumulation of SMCs in early human atherosclerotic lesions...
  17. ncbi Extensive deposits of complement C3d and C5b-9 in the choriocapillaris of eyes of patients with diabetic retinopathy
    Verena B Gerl
    Department of Ophthalmology, University of Mainz, Mainz, Germany
    Invest Ophthalmol Vis Sci 43:1104-8. 2002
    ..To determine the presence of activated complement components in eyes affected by diabetic retinopathy...
  18. ncbi Cellular response to injury in membranous nephropathy
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
    J Am Soc Nephrol 16:1195-204. 2005
    ..Improved understanding of the role of complement in the pathogenesis of MN and of the cellular response to C5b-9 attack creates several new opportunities for therapeutic intervention that may benefit patients with MN in the future...
  19. ncbi Glycation inactivation of the complement regulatory protein CD59: a possible role in the pathogenesis of the vascular complications of human diabetes
    Xuebin Qin
    Hematology Division, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Diabetes 53:2653-61. 2004
    ..We conclude that glycation inactivation of hCD59 that leads to increased MAC deposition may contribute to the extensive vascular pathology that complicates human diabetes...
  20. ncbi Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense
    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, Netherlands
    Science 317:1552-4. 2007
    ..Proteins of the complement membrane attack complex (MAC) and the protein perforin share a common MACPF domain that is responsible for membrane ..
  21. pmc Inhibition of the complement membrane attack complex by Schistosoma mansoni paramyosin
    Jiusheng Deng
    Departments of Human Microbiology Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    Infect Immun 71:6402-10. 2003
    ..Taken together, these findings suggest that an exogenous form of S. mansoni paramyosin inhibits activation of the terminal pathway of complement and thus has an important immunomodulatory role in schistosomiasis...
  22. ncbi Sublytic terminal complement attack induces c-fos transcriptional activation in myotubes
    Tudor D Badea
    Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Neuroimmunol 142:58-66. 2003
    ..We propose that c-fos gene transcription associated with myotube dedifferentiation is induced by C5b-9 through ERK1-mediated assembly of serum response factor-ternary complex...
  23. ncbi Interaction between the C8 alpha-gamma and C8 beta subunits of human complement C8: role of the C8 beta N-terminal thrombospondin type 1 module and membrane attack complex/perforin domain
    Primrose Musingarimi
    Department of Chemistry and Biochemistry and School of Medicine, University of South Carolina, Columbia, South Carolina 29208, USA
    Biochemistry 41:11255-60. 2002
    ..Results from activity assays suggest that residues within this segment also mediate binding and incorporation of C8 into the MAC...
  24. pmc Enhanced complement activation is part of the unfavourable cardiovascular risk profile in South Asians
    M A Siezenga
    Leiden University Medical Center, Department of Nephrology, Leiden, The Netherlands
    Clin Exp Immunol 157:98-103. 2009
    ..4, 95% confidence interval 1.8-15.8). These results suggest that enhanced complement activation is part of the unfavourable cardiovascular risk profile in South Asians...
  25. pmc Predominant role for C5b-9 in renal ischemia/reperfusion injury
    W Zhou
    Department of Nephrology and Transplantation, Guy s Hospital, London, United Kingdom
    J Clin Invest 105:1363-71. 2000
    ..The membrane attack complex of complement is a potential target for prevention of I/R injury in this model...
  26. ncbi Role of complement and complement membrane attack complex in laser-induced choroidal neovascularization
    Puran S Bora
    Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, 301E Muhammad Ali Boulevard, Louisville, KY 40202, USA
    J Immunol 174:491-7. 2005
    ..It is possible that a similar mechanism may be involved in the pathophysiology of other angiogenesis essential diseases...
  27. ncbi Glomerular deposition and urinary excretion of complement factor H in idiopathic membranous nephropathy
    Morito Endo
    Division of Nephrology, Internal Medicine II, Nihon University School of Medicine, Tokyo, Japan
    Nephron Clin Pract 97:c147-53. 2004
    ....
  28. ncbi Factor H-related protein-5: a novel component of human glomerular immune deposits
    Brendan Murphy
    Department of Nephrology, St Vincent s Hospital, Melbourne, Victoria, Australia
    Am J Kidney Dis 39:24-7. 2002
    ..This study shows FHR-5 to be strongly associated with glomerular complement deposition and suggests a role in complement activation or regulation. It may be an important mediator of glomerular disease...
  29. ncbi Critical protection from renal ischemia reperfusion injury by CD55 and CD59
    Koei Yamada
    Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Immunol 172:3869-75. 2004
    ..Our findings suggest a rationale for anti-complement therapies aimed at preventing microvascular injury during ischemia reperfusion, and the CD55(-/-)CD59(-/-) mouse provides a useful animal model in this regard...
  30. ncbi Both apoptosis and complement membrane attack complex deposition are major features of murine acute graft-vs.-host disease
    Florin Niculescu
    Department of Medicine, Division of Rheumatology and Clinical Immunology, Baltimore, MD 21201, USA
    Exp Mol Pathol 79:136-45. 2005
    ..These results indicate a role for both adaptive immunity and innate immunity in this model of GVHD and support its use in modeling human acute GVHD in the nonmyeloablative setting...
  31. pmc A non membrane-targeted human soluble CD59 attenuates choroidal neovascularization in a model of age related macular degeneration
    Siobhan M Cashman
    Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, United States of America
    PLoS ONE 6:e19078. 2011
    ..We propose that the above approaches warrant further exploration as potential approaches for alleviating complement mediated damage to ocular tissues in AMD...
  32. pmc Decay accelerating factor (CD55)-mediated attenuation of complement: therapeutic implications for age-related macular degeneration
    Kelly N Ma
    Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02111, USA
    Invest Ophthalmol Vis Sci 51:6776-83. 2010
    ..Here the investigators test the hypothesis that increasing the expression of decay accelerating factor (CD55) on RPE cells may result in reduced MAC-mediated damage...
  33. doi Complement regulator CD59 protects against atherosclerosis by restricting the formation of complement membrane attack complex
    Gongxiong Wu
    Department of Medicine, Brigham and Women s Hospital, Laboratory forTranslational Research, Harvard Medical School, Cambridge, MA 02139, USA
    Circ Res 104:550-8. 2009
    ..CD59 is a key regulator of complement membrane attack complex (MAC) assembly...
  34. doi Complement membrane attack complex formation and infectivity of Trichinella spiralis and T. nativa in rats
    Anu Näreaho
    Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
    Vet Parasitol 159:263-7. 2009
    ..nativa have efficient mechanisms to protect themselves against complement attack. The difference in infectivity for rats between the two species, however, is not due to a differential resistance to complement membrane attack complex.
  35. doi Evaluation of adenovirus-delivered human CD59 as a potential therapy for AMD in a model of human membrane attack complex formation on murine RPE
    Kasmir Ramo
    Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, USA
    Invest Ophthalmol Vis Sci 49:4126-36. 2008
    ....
  36. ncbi Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy
    M Endo
    Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
    Nephrol Dial Transplant 13:1984-90. 1998
    ..The present study was undertaken to elucidate whether the lectin pathway was involved in the pathogenic mechanism of IgA-N...
  37. ncbi Crystal structure of complement protein C8gamma in complex with a peptide containing the C8gamma binding site on C8alpha: implications for C8gamma ligand binding
    Leslie L Lovelace
    Department of Chemistry and Biochemistry and School of Medicine, University of South Carolina, Columbia, SC 29208, United States
    Mol Immunol 45:750-6. 2008
    ..These results suggest a role for C8alpha in regulating access to the putative C8gamma ligand binding site...
  38. ncbi Terminal complement complex C5b-9-treated human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization
    Yongwen Chen
    Laboratory of Immunoregulation, Institute of Immunology, PLA, The Third Military Medical University, Chongqing, P R China
    Eur J Immunol 37:167-76. 2007
    ..Our results are the first to report that DC are potential immunoregulatory targets of C5b-9, suggesting that C5b-9 bridges innate and acquired immunity by inducing DC maturation...
  39. ncbi C5b-9 complement complex in autoimmune demyelination and multiple sclerosis: dual role in neuroinflammation and neuroprotection
    Horea Rus
    University of Maryland at Baltimore, School of Medicine, Department of Neurology, 655 W Baltimore Street, BRB 12 016, Baltimore, MD 21201, USA
    Ann Med 37:97-104. 2005
    ..These findings indicate that activation of complement C5b-9 plays a pro-inflammatory role in the acute phase of the disease, but may also be neuroprotective during the chronic phase of the disease...
  40. pmc Involvement of the ERK mitogen-activated protein kinase in cell resistance to complement-mediated lysis
    S Kraus
    Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    Clin Exp Immunol 123:366-74. 2001
    ..In conclusion, cell desensitization by sublytic doses of the complement membrane attack complex involves a signalling cascade that includes PKC-mediated ERK activation.
  41. ncbi Incorporation of human complement C8 into the membrane attack complex is mediated by a binding site located within the C8beta MACPF domain
    Charity L Brannen
    Department of Chemistry and Biochemistry and the School of Medicine, University of South Carolina, Columbia, South Carolina 29208, USA
    Mol Immunol 44:960-5. 2007
    ..Furthermore, results indicate the principal binding sites for C8alpha and C5b-7 are located within this domain, and that C8beta binding specificity is not determined by the N- and C-terminal modules...
  42. doi Generation and phenotyping of mCd59a and mCd59b double-knockout mice
    Xuebin Qin
    Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Am J Hematol 84:65-70. 2009
    ..We report here that total abrogation of mCd59 function in mCd59ab(-/-) mice results in complement-mediated hemolytic anemia that is rescued by the deficiency of C3 in compound mCd59ab(-/-)/C3(-/-) mice...
  43. pmc Crystal structure of the MACPF domain of human complement protein C8 alpha in complex with the C8 gamma subunit
    Daniel J Slade
    Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208, USA
    J Mol Biol 379:331-42. 2008
    ..Also observed is structural conservation of the MACPF signature motif Y/W-G-T/S-H-F/Y-X(6)-G-G in alphaMACPF and Plu-MACPF, and conservation of several key glycine residues known to be important for refolding and pore formation by CDCs...
  44. ncbi Central role of complement membrane attack complex in monosodium urate crystal-induced neutrophilic rabbit knee synovitis
    Nicole Tramontini
    Pfizer Global Research and Development, Ann Arbor, Michigan, USA
    Arthritis Rheum 50:2633-9. 2004
    ..Hence, we studied rabbits deficient in the MAC component C6 to determine if MAC mediated urate crystal-induced arthritis...
  45. ncbi Binding of human complement C8 to C9: role of the N-terminal modules in the C8 alpha subunit
    Jeffery J Scibek
    Department of Chemistry and Biochemistry and School of Medicine, University of South Carolina, Columbia, South Carolina 29208, USA
    Biochemistry 41:14546-51. 2002
    ..These results indicate that both N-terminal modules in C8alpha have a role in forming the principal binding site for C9 and that binding may be dependent on a cooperative interaction between these modules and the C8alpha MACPF domain...
  46. pmc CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells
    A Davies
    MRC Molecular Immunopathology Unit, MRC Centre, Cambridge, United Kingdom
    J Exp Med 170:637-54. 1989
    ....
  47. ncbi Functional characterization of the lectin pathway of complement in human serum
    Anja Roos
    Department of Nephrology, C3P, Leiden University Medical Center, P O Box 9600, 2300 RC, Leiden, The Netherlands
    Mol Immunol 39:655-68. 2003
    ..This assay offers novel possibilities for patient diagnostics as well as for the study of disease association with the LP...
  48. ncbi CD59a is the primary regulator of membrane attack complex assembly in the mouse
    Sivasankar Baalasubramanian
    Complement Biology Group, Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Cardiff, United Kingdom
    J Immunol 173:3684-92. 2004
    ..Erythrocyte CD59b did not inhibit complement lysis except when CD59a was absent or blocked. These data confirm that CD59a is the primary regulator of complement membrane attack in mouse...
  49. ncbi Intracerebroventricular injection of the terminal complement complex causes inflammatory reaction in the rat brain
    Claudia Casarsa
    Department of Physiology and Pathology, University of Trieste, Trieste, Italy
    Eur J Immunol 33:1260-70. 2003
    ..Elevated concentration of IL-1 beta was also found in the cerebrospinal fluid and in periventricular areas of rats treated with TCC...
  50. ncbi Complement activation in angiotensin II-induced organ damage
    Erdenechimeg Shagdarsuren
    Medical Faculty of the Charite, Franz Volhard Clinic, and HELIOS Klinikum Berlin, Germany
    Circ Res 97:716-24. 2005
    ..VSMC from dTGR are more sensitive for C3 activation. Our data show that, in this Ang II-induced model, complement activation is a major participant and suggest that TNF-alpha and CRP may play a role in its induction...
  51. ncbi CD59a deficiency exacerbates accelerated nephrotoxic nephritis in mice
    Daniel Turnberg
    Rheumatology Section and Department of Histopathology, Faculty of Medicine, Hammersmith Campus, Imperial College, London
    J Am Soc Nephrol 14:2271-9. 2003
    ..The lack of CD59a, by allowing unregulated MAC deposition, exacerbates the renal injury in this model of immune complex-mediated glomerulonephritis...
  52. pmc Decay-accelerating factor suppresses complement C3 activation and retards atherosclerosis in low-density lipoprotein receptor-deficient mice
    Viola W Y Leung
    Vascular Science Section, Imperial College, National Heart and Lung Institute, the Division of Investigative Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom
    Am J Pathol 175:1757-67. 2009
    ..Because upstream complement activation is potentially protective, this study underlines the importance of DAF in shielding the arterial wall from the atherogenic effects of complement...
  53. ncbi The architectural transition of human complement component C9 to poly(C9)
    R G DiScipio
    La Jolla Institute for Experimental Medicine, CA 92037, USA
    Mol Immunol 36:575-85. 1999
    ..As a consequence of circular polymerization the midsection of the polypeptide chain becomes exposed as each C9 lengths to fashion a volute form. reserved...
  54. ncbi C5b-9 terminal complement complex assembly on apoptotic cells in human arterial wall with atherosclerosis
    Florin Niculescu
    Department of Pathology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
    Exp Mol Pathol 76:17-23. 2004
    ..In conclusion, some apoptotic cells carry C5b-9 deposits, suggesting that complement might be activated by apoptotic cells and involved in the promotion of apoptosis, contributing to the progression of atherosclerotic lesions...
  55. pmc CD59a deficiency exacerbates ischemia-reperfusion injury in mice
    Daniel Turnberg
    Rheumatology Section, Eric Bywaters Centre, London, United Kingdom
    Am J Pathol 165:825-32. 2004
    ....
  56. ncbi Effects of membrane attack complex of complement on apoptosis in experimental autoimmune encephalomyelitis
    Teodora Niculescu
    University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA
    Ann N Y Acad Sci 1010:530-3. 2003
    ..These results indicate that C5 and possibly MAC may be required for the limitation of inflammatory response within the central nervous system...
  57. ncbi Neonatal porcine Sertoli cells inhibit human natural antibody-mediated lysis
    Jannette M Dufour
    Surgical Medical Research Institute, University of Alberta, Edmonton, Alberta, Canada
    Biol Reprod 72:1224-31. 2005
    ..This suggests that NPSCs may be able to survive humoral-mediated rejection in a clinical situation...
  58. ncbi C6 mediates chronic progression of tubulointerstitial damage in rats with remnant kidneys
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    J Am Soc Nephrol 13:928-36. 2002
    ..Treatment to reduce C5b-9 attack in tubular cells may slow progression and facilitate recovery...
  59. ncbi Comparison of two laboratory methods for the determination of serum resistance in Borrelia burgdorferi isolates
    P Kraiczy
    Institute of Medical Microbiology, University Hospital, Frankfurt, Germany
    Immunobiology 201:406-19. 2000
    ..The IFA, however, is regarded as superior to the GIA owing to the obvious ease of performance and its rapid capability for the classification of even very slow growing isolates...
  60. ncbi Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury
    P F Stahel
    Department of Surgery, University Hospital, Zurich, Switzerland
    J Neurotrauma 18:773-81. 2001
    ..998; p < 0.05). These data demonstrate for the first time that terminal pathway complement activation occurs after head injury and suggest a possible pathophysiological role of complement with regard to posttraumatic BBB dysfunction...
  61. ncbi Insights into the human CD59 complement binding interface toward engineering new therapeutics
    Yuxiang Huang
    Department of Microbiology and Immunology, Medical University of South Carolina, South Carolina 29403, USA
    J Biol Chem 280:34073-9. 2005
    ..Based on the enhanced activity of membrane-bound mutant CD59 molecules, clinically relevant soluble mutant CD59-based proteins were prepared and shown to have up to a 3-fold increase in complement inhibitory activity...
  62. ncbi C5b-9 does not mediate chronic tubulointerstitial disease in the absence of proteinuria
    Gopala K Rangan
    Division of Nephrology, University of Washington Medical Center, Seattle, Washington, USA
    Kidney Int 67:492-503. 2005
    ..Here, we examined whether C5b-9 has a pathogenic role in tubulointerstitial disease in the absence of proteinuria...
  63. ncbi Beyond lysis: how complement influences cell fate
    Duncan S Cole
    Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK
    Clin Sci (Lond) 104:455-66. 2003
    ..Here we review some of these non-classical activities of complement and stress the roles that they may play in maintaining the integrity of the organism...
  64. ncbi CD59, a complement regulatory protein, controls choroidal neovascularization in a mouse model of wet-type age-related macular degeneration
    Nalini S Bora
    Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Immunol 178:1783-90. 2007
    ..Thus, our results suggest that the inhibition of complement by soluble CD59 may provide a novel therapeutic alternative to current treatment...
  65. pmc Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction
    M Meuwissen
    Department of Cardiology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
    J Clin Pathol 59:196-201. 2006
    ..C reactive protein (CRP), an important serum marker of atherosclerotic vascular disease, has recently been reported to be active inside human atherosclerotic plaques...
  66. ncbi Treatment with an inhibitory monoclonal antibody to mouse factor B protects mice from induction of apoptosis and renal ischemia/reperfusion injury
    Joshua M Thurman
    Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA, and Department of Pathology, University Hospital Dubrava, Zabreb, Croatia
    J Am Soc Nephrol 17:707-15. 2006
    ..Thus, use of an inhibitory mAb to mouse factor B effectively prevented activation of complement in the kidney after I/R and protected the mice from necrotic and apoptotic injury of the tubules...
  67. ncbi Anti-disialoside antibodies kill perisynaptic Schwann cells and damage motor nerve terminals via membrane attack complex in a murine model of neuropathy
    Susan K Halstead
    Division of Clinical Neurosciences, Institute of Neurological Sciences, University of Glasgow Southern General Hospital, Glasgow G51 4TF, UK
    Brain 127:2109-23. 2004
    ..This is the first demonstration that complement mediated pSC injury occurs in a model of autoimmune neuropathy and provides a rationale for investigating the possibility of pSC injury in equivalent conditions in man...
  68. ncbi Terminal complement complex in septic shock with capillary leakage: marker of complement activation?
    T Schuerholz
    Friedrich Schiller University, Department of Anaesthesiology and Intensive Care, Jena, Germany
    Eur J Anaesthesiol 22:541-7. 2005
    ..The aim of this study was to evaluate the value of terminal complement complex (C5b-9) plasma levels as a marker for complement activation in septic shock with concomitant capillary leak syndrome...
  69. ncbi Letter in response to A. Agrawal: 'CRP after 2004'
    Carmen W van den Berg
    Mol Immunol 43:292-3. 2006
  70. ncbi Recent advances on the complement system of teleost fish
    H Boshra
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 413 Rosenthal, 3800 Spruce St, Philadelphia, PA 19104, USA
    Fish Shellfish Immunol 20:239-62. 2006
    ..Such studies will be pivotal in providing new insights into complement-related mechanisms of recognition and defense that are essential to maintaining fish homeostasis...
  71. ncbi Disodium Disuccinate Astaxanthin (Cardax) attenuates complement activation and reduces myocardial injury following ischemia/reperfusion
    D Adam Lauver
    Department of Pharmacology, University of Michigan Medical School, 1301C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA
    J Pharmacol Exp Ther 314:686-92. 2005
    ....
  72. ncbi Local production of complement proteins in rheumatoid arthritis synovium
    Elena Neumann
    University of Regensburg, Regensburg, Germany
    Arthritis Rheum 46:934-45. 2002
    ..This study was undertaken to characterize the expression of complement proteins and receptors in RA SF and ST...
  73. ncbi The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions
    Bianca P Brink
    Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
    J Neuropathol Exp Neurol 64:147-55. 2005
    ..In contrast, in the purely cortical lesions, the extent of complement deposition in general was low. In conclusion, the role of complement in MS pathogenesis seems lesion location-dependent...
  74. ncbi Soluble human complement receptor 1 limits ischemic damage in cardiac surgery patients at high risk requiring cardiopulmonary bypass
    Harold L Lazar
    Department of Cardiothoracic Surgery, Boston University School of Medicine and Boston Medical Center, Boston, Mass 02118, USA
    Circulation 110:II274-9. 2004
    ....
  75. ncbi Intraglomerular synthesis of complement C3 and its activation products in IgA nephropathy
    K Abe
    Second Department of Internal Medicine, Nagasaki University School of Medicine, 1 7 1, Sakamoto, Nagasaki 852 5201, Japan
    Nephron 87:231-9. 2001
    ....
  76. ncbi The membrane attack complex of complement induces caspase activation and apoptosis
    Alma J Nauta
    Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Immunol 32:783-92. 2002
    ..Apoptosis as a consequence of complement-mediated cell damage may provide an explanation for the presence of apoptosis in inflammatory processes, for instance in hyperacute xenograft rejection...
  77. pmc Complement activation in infective endocarditis: correlation with extracardiac manifestations and prognosis
    I J Messias-Reason
    Laboratory of Immunopathology, Department of Pathology, Clinical Hospital of Federal University of Paraná, Curitiba, Brazil
    Clin Exp Immunol 127:310-5. 2002
    ..02). Our data demonstrate the activation of the complement classical pathway, most probably mediated by CIC, in IE and suggests C3d and C3adesArg as possible markers for extracardiac lesion and severity of the disease...
  78. ncbi Possible mechanism for medial smooth muscle cell injury in diabetic nephropathy: glycoxidation-mediated local complement activation
    Noriko Uesugi
    Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan
    Am J Kidney Dis 44:224-38. 2004
    ..We focused on medial smooth muscle cell (SMC) injury and the involvement of glycoxidation and complement activation...
  79. ncbi [Inhibitory effect of hDAF displayed on yeast cells on deposition of complement on the yeast cells]
    Bo Guo
    Department of Immunology, Third Military Medical University, Chongqing 400038, China
    Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 20:269-71. 2004
    ..To investigate whether the hDAF displayed on the surface of yeast cells can inhibit the deposition of C5b-9...
  80. ncbi Complement activation in diabetic ketoacidosis brains
    William H Hoffman
    Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA
    Exp Mol Pathol 80:283-8. 2006
    ....
  81. ncbi [Membranous glomerulonephritis (membranous nephropathy): Pathogenesis, pathophysiology, and therapy]
    Teiko Ohashi
    Fourth Department of Internal Medicine, Kidney Center, Tokyo Women s Medical University
    Nihon Rinsho 64:417-21. 2006
  82. doi Subversion of complement activation at the bacterial surface promotes serum resistance and opsonophagocytosis of Francisella tularensis
    Abdelhakim Ben Nasr
    Department of Microbiology and Immunology, Medical Research Building, University of Texas Medical Branch, Galveston, TX, USA
    J Leukoc Biol 84:77-85. 2008
    ..C3b inactivation also leads to inefficient MAC assembly, which contributes to the ability of this bacterium to resist complement lysis...
  83. pmc A protein toxin from the sea anemone Phyllodiscus semoni targets the kidney and causes a severe renal injury with predominant glomerular endothelial damage
    Masashi Mizuno
    Department of Nephrology, Nagoya University Graduate School of Medicine, Japan
    Am J Pathol 171:402-14. 2007
    ..The demonstration that PsTX-T and PsTX-115 were highly nephrotoxic acting via induction of complement activation suggests that inhibition of complement might be used to prevent acute renal damage following envenomation by P. semoni...
  84. ncbi Complement activation in experimental human malaria infection
    Meta Roestenberg
    Radboud University Nijmegen Medical Center, Postbus 9101, 6500 HB Nijmegen, The Netherlands
    Trans R Soc Trop Med Hyg 101:643-9. 2007
    ..Treatment with artemether/lumefantrine was followed by classical and alternative pathway complement activation, without evidence for mannan-binding-lectin-mediated complement activation...
  85. ncbi [The role of complement in physiology and pathology]
    Izabela Klaska
    Centrum Biologii Medycznej, Polska Akademia Nauk, Łódź, Poland
    Postepy Hig Med Dosw (Online) 61:167-77. 2007
    ....
  86. ncbi Decay-accelerating factor but not CD59 limits experimental immune-complex glomerulonephritis
    Lihua Bao
    Section of Nephrology, The University of Chicago, Chicago, IL 60637, USA
    Lab Invest 87:357-64. 2007
    ..Our findings suggest that activation of C3 is strongly associated with experimental ICGN while downstream formation of C5b-9 is of lesser pathogenic importance in this model...
  87. ncbi A case of renal sarcoidosis with complement activation via the lectin pathway
    Shinji Hagiwara
    Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan
    Am J Kidney Dis 45:580-7. 2005
    ..From this case of renal sarcoidosis, it is hypothesized that P acnes may be involved in pathogenesis of granulomatous interstitial nephritis and that it plays a role in glomerular complement activation via the lectin pathway...
  88. pmc The membrane attack pathway of complement drives pathology in passively induced experimental autoimmune myasthenia gravis in mice
    B P Morgan
    Department of Pathology, School of Medicine, Cardiff University, Cardiff, UK
    Clin Exp Immunol 146:294-302. 2006
    ..These findings provoke us to suggest that current anti-C therapeutics targeting MAC assembly will be beneficial in MG patients resistant to conventional therapies...
  89. ncbi The complement system in central nervous system diseases
    Horea Rus
    Department of Neurology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
    Autoimmunity 39:395-402. 2006
    ..These findings strongly suggest that complement activation and membrane assembly of C5b-9 can play a role in injury but can also provide neuroprotection depending on the pathophysiological context...
  90. ncbi Complement activation during sepsis in humans
    Heike Schreiber
    Dept of Traumatology, Hand, Plastic, and Reconstructive Surgery, Steinhoevelstr 9, 89075 Ulm, Germany
    Adv Exp Med Biol 586:217-26. 2006
  91. ncbi C5b-9 complement complex in autoimmune demyelination: dual role in neuroinflammation and neuroprotection
    Horea Rus
    Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
    Adv Exp Med Biol 586:139-51. 2006
  92. ncbi Retinal synthesis and deposition of complement components induced by ocular hypertension
    Markus H Kuehn
    Department of Ophthalmology and Visual Sciences, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA
    Exp Eye Res 83:620-8. 2006
    ..The results show that complement activation occurs in the retina that has been subjected to elevated IOP, and may have implications in pathophysiology of glaucoma...
  93. ncbi Comparison of inflammatory responses after off-pump and on-pump coronary surgery using surface modifying additives circuit
    Janine M Quaniers
    Department of Surgery, Biostatistics, University of Liege, Liege, Belgium
    Ann Thorac Surg 81:1683-90. 2006
    ..Because of the central role of extracorporeal circulation (EC), off-pump coronary bypass surgery is deemed preferable. Do different modalities of EC challenge this view?..
  94. ncbi Terminal complement complex (C5b-9) in children with recurrent hemolytic uremic syndrome
    Friederike Prüfer
    Universitäts Klinik für Kinder und Jugendheilkunde, Innsbruck, Austria
    Semin Thromb Hemost 32:121-7. 2006
    ..This may play an important role in the inferior outcome of these patients. The isolated substitution of factor H, or other complement inhibitors to block TCC formation, may represent useful therapies for these patients...
  95. ncbi Pathological study on the relationship between C4d, CD59 and C5b-9 in acute renal allograft rejection
    S Nishi
    Blood Purification Center, Niigata University Hospital, Niigata City, Japan
    Clin Transplant 18:18-23. 2004
    ..The substantially expressed CD59 on PTC may affect this dissociation between C4d and C5b-9 on PTC. The intensive deposition of C5b-9 on TBM in acute rejection cases may suggest an independent immunological injury attacking tubular cells...
  96. ncbi Complement function in mAb-mediated cancer immunotherapy
    Kyra A Gelderman
    Department of Pathology L1 Q, Leiden University Medical Center, Postbox 9600, 2300 RC Leiden, The Netherlands
    Trends Immunol 25:158-64. 2004
  97. pmc Herpes simplex virus 1 infected neuronal and skin cells differ in their susceptibility to complement attack
    Riina Rautemaa
    Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki and the Helsinki University Central Hospital, Finland
    Immunology 106:404-11. 2002
    ..This may contribute to the persistence of a latent HSV-1 infection in neuronal cells for prolonged periods...
  98. ncbi Serum anti-cholesterol antibodies in chronic hepatitis-C patients during IFN-alpha-2b treatment
    Adrienn Biro
    3rd Department of Medicine, Semmelweis University, Budapest, Hungary
    Immunobiology 207:161-8. 2003
    ..The correlation between the ACHA and C5b-9 levels indicate, that the ACHA may play a role in the complement activation in CHC...
  99. ncbi Crry, but not CD59 and DAF, is indispensable for murine erythrocyte protection in vivo from spontaneous complement attack
    Takashi Miwa
    Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Blood 99:3707-16. 2002
    ..Our results raise the possibility that proper control of C3 activation may also be critical on human erythrocytes, where CR1 but not DAF could be the principal regulator of spontaneous C3 activation...
  100. ncbi Mechanism of complement activation during extracorporeal blood-biomaterial interaction: effects of heparin coated and uncoated surfaces
    Ruedger Kopp
    Institute of Physiology, University Hospital Aachen, Germany
    ASAIO J 48:598-605. 2002
    ..Increased binding of complement regulators to HBS appears to effectively reduce complement activation by biomaterials, leading to improved long-term biocompatibility...
  101. pmc Effects of C-reactive protein and pentosan polysulphate on human complement activation
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Immunology 106:381-8. 2002
    ..Pentosan polysulphate (PPS), an orally active agent, blocked C activation in the same concentration range of 1-1000 microg/ml as heparin, dextran sulphate, compstatin and fucoidan. PPS may have practical application as a C inhibitor...

Research Grants75

  1. LUNG INJURY BY OXYGEN METABOLITES
    Peter Ward; Fiscal Year: 2004
    ..These studies should extend our understanding of the roles of complement activation products in acute lung injury. ..
  2. MECHANISMS OF COMPLEMENT INDUCED MYOCARDIAL ISCHEMIA
    GREGORY STAHL; Fiscal Year: 2007
    ..abstract_text> ..
  3. Complement Activation on Neisseria meningitidis
    Sanjay Ram; Fiscal Year: 2010
    ..The studies proposed in this application will help us better understand how this pathogen escapes killing by complement and will ultimately aid in the development of better vaccines against meningococcal meningitis. ..
  4. MECHANISMS OF COMPLEMENT INDUCED ENDOTHELIAL DYSFUNCTION
    GREGORY STAHL; Fiscal Year: 2007
    ..abstract_text> ..
  5. Anti-Properdin MoAb as a novel therapeutics for arthritis
    REKHA BANSAL; Fiscal Year: 2007
    ..NovelMed has filed a patent on such inhibitors and additional patents are in preparation. ..
  6. BIOLOGY OF DECAY ACCELERATING FACTOR
    Wenchao Song; Fiscal Year: 2004
    ..These studies will not only establish a physiological role of DAF in autoimmune reactions but also will shed light on the debate concerning the role of complement in autoimmune diseases. ..
  7. PATHOGENESIS OF TRANSPLANT-ASSOCIATED ARTERIOSCLEROSIS
    Peter Libby; Fiscal Year: 1993
    ..methods to seek evidence for serological reactions in situ as well as for assembly of the complement membrane attack complex. b) We will examine sera and vessels from transplant recipients for the presence of antibodies ..
  8. Role of C5a versus C5b-9 in Myocardial Ischemia and Reperfusion Injury
    Benjamin Guikema; Fiscal Year: 2007
    ..Drugs currently available may be better used to protect the heart from damage following a heart attack. ..
  9. Improving Kidney Transplant Outcome with a Novel Complement Inhibitor
    SHELLEY MAVES; Fiscal Year: 2007
    ..Eventually, this therapeutic could also be used to treat acute and chronic humoral rejection, glomerulonephritis and other autoimmune diseases. ..
  10. Complement Regulatory Proteins and Autoimmune Disease
    Wenchao Song; Fiscal Year: 2006
    ..These studies will increase our understanding of the pathogenesis of complement-mediatedautoimmune injury and facilitate the development of complement-based therapeutic strategies. ..
  11. COMPLEMENT C5 AND C5A RECEPTOR--MOLECULAR GENETICS
    RICK WETSEL; Fiscal Year: 1999
    ....
  12. ELECTRON MICROSCOPY OF MYOPATHIES
    Andrew Engel; Fiscal Year: 1990
    ..and prenecrotic muscle fibers will be studied to define the ultrastructural binding site of the complement membrane attack complex. The pathogenesis of inflammatory myopathies will be investigated by monoclonal antibody analysis of ..
  13. Innate Immunity in Gastrointestinal Ischemia
    Melanie Hart; Fiscal Year: 2006
    ..The specific aims are as follows: 1) characterize the complement pathways involved in G/JR and 2) determine the role of complement in apoptosis following GI/R. ..
  14. Targeting complement inhibitors to the human proximal tubule
    Richard Quigg; Fiscal Year: 2007
    ..The work proposed here uses modern technology to design treatment for these disorders. Although these are considered pilot and high-risk studies, successful completion could give us treatments for immediate use in clinical studies. ..
  15. DISTAL COMPLEMENT COMPONENTS IN IMMUNE RENAL INJURY
    William Couser; Fiscal Year: 1990
    ..Studies in experimental models of MN induced by both of these mechanisms have documented that the complement membrane attack complex, C5b-9, mediates proteinuria in MN, presumably through insertion into the GEC membrane...
  16. MECHANISMS OF COMPLEMENT INDUCED ENDOTHELIAL DYSFUNCTION
    GREGORY STAHL; Fiscal Year: 2004
    ..The studies will demonstrate that specific inhibition of MBL binding will decrease complement activation and tissue injury following gastrointestinal ischemia and reperfusion. ..
  17. PLATELET LEUKOCYTE PHYSIOLOGY IN CARDIOPULMONARY BYPASS
    Brian Smith; Fiscal Year: 2001
    ..The long term goals of these studies is to develop therapeutic strategies to alleviate complications of extracorporeal circulation and to understand the basic biology of platelet-white blood cell-erthyrocyte-endothelial interactions. ..