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| complement membrane attack complexSummarySummary: 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
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Publications
CD59 efficiently protects human NT2-N neurons against complement-mediated damageE 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...
Complement-associated deposits in the human retinaAditya 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...
Complement regulator CD59 protects against atherosclerosis by restricting the formation of complement membrane attack complexGongxiong 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...
Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defenseMichael 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 ..
Evaluation of adenovirus-delivered human CD59 as a potential therapy for AMD in a model of human membrane attack complex formation on murine RPEKasmir Ramo
Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, USA
Invest Ophthalmol Vis Sci 49:4126-36. 2008....
Extensive deposits of complement C3d and C5b-9 in the choriocapillaris of eyes of patients with diabetic retinopathyVerena 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...
Both apoptosis and complement membrane attack complex deposition are major features of murine acute graft-vs.-host diseaseFlorin 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...
Incorporation of human complement C8 into the membrane attack complex is mediated by a binding site located within the C8beta MACPF domainCharity 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...
C5b-9 complement complex in autoimmune demyelination and multiple sclerosis: dual role in neuroinflammation and neuroprotectionHorea 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...
Decay accelerating factor (CD55)-mediated attenuation of complement: therapeutic implications for age-related macular degenerationKelly 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...
Crystal structure of complement protein C8gamma in complex with a peptide containing the C8gamma binding site on C8alpha: implications for C8gamma ligand bindingLeslie 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...
Generation and phenotyping of mCd59a and mCd59b double-knockout miceXuebin 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...
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 domainPrimrose 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...
Complement membrane attack complex formation and infectivity of Trichinella spiralis and T. nativa in ratsAnu 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.
A non membrane-targeted human soluble CD59 attenuates choroidal neovascularization in a model of age related macular degenerationSiobhan 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...
A common fold mediates vertebrate defense and bacterial attackCarlos 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...
Inhibition of the complement membrane attack complex by Schistosoma mansoni paramyosinJiusheng 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...
C5b-9 does not mediate chronic tubulointerstitial disease in the absence of proteinuriaGopala 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...
Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injuryP 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...
C6 mediates chronic progression of tubulointerstitial damage in rats with remnant kidneysMasaomi 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...
Intracerebroventricular injection of the terminal complement complex causes inflammatory reaction in the rat brainClaudia 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...
Neonatal porcine Sertoli cells inhibit human natural antibody-mediated lysisJannette 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...
Glycation inactivation of the complement regulatory protein CD59: a possible role in the pathogenesis of the vascular complications of human diabetesXuebin 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...
Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegenerationZhi 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...
Functional characterization of the lectin pathway of complement in human serumAnja 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...
CD59a deficiency exacerbates accelerated nephrotoxic nephritis in miceDaniel 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...
C5b-9 terminal complement complex assembly on apoptotic cells in human arterial wall with atherosclerosisFlorin 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...
Effects of membrane attack complex of complement on apoptosis in experimental autoimmune encephalomyelitisTeodora 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...
CD59a deficiency exacerbates ischemia-reperfusion injury in miceDaniel Turnberg
Rheumatology Section, Eric Bywaters Centre, London, United Kingdom
Am J Pathol 165:825-32. 2004....
Central role of complement membrane attack complex in monosodium urate crystal-induced neutrophilic rabbit knee synovitisNicole Tramontini
Pfizer Global Research and Development, Ann Arbor, Michigan, USA
Arthritis Rheum 50:2633-9. 2004..C6 and MAC activation may represent novel therapeutic targets for suppression of neutrophil-mediated joint inflammation in gout...
Binding of human complement C8 to C9: role of the N-terminal modules in the C8 alpha subunitJeffery 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...
The tick salivary protein Salp15 inhibits the killing of serum-sensitive Borrelia burgdorferi sensu lato isolatesTim 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...
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...
Decay-accelerating factor suppresses complement C3 activation and retards atherosclerosis in low-density lipoprotein receptor-deficient miceViola 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...
The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injuryConstantino 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...
CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cellsA Davies
MRC Molecular Immunopathology Unit, MRC Centre, Cambridge, United Kingdom
J Exp Med 170:637-54. 1989....
Insights into the human CD59 complement binding interface toward engineering new therapeuticsYuxiang 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...
CD59a is the primary regulator of membrane attack complex assembly in the mouseSivasankar 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...
Complement activation in angiotensin II-induced organ damageErdenechimeg Shagdarsuren
Medical Faculty of the Charit, 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...
Comparison of two laboratory methods for the determination of serum resistance in Borrelia burgdorferi isolatesP 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...
Critical protection from renal ischemia reperfusion injury by CD55 and CD59Koei 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...
CD59, a complement regulatory protein, controls choroidal neovascularization in a mouse model of wet-type age-related macular degenerationNalini 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...
Role of complement and complement membrane attack complex in laser-induced choroidal neovascularizationPuran 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...
Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarctionM 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...
Cellular response to injury in membranous nephropathyMasaomi 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...
Crystal structure of the MACPF domain of human complement protein C8 alpha in complex with the C8 gamma subunitDaniel 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...
Effects of complement C5 on apoptosis in experimental autoimmune encephalomyelitisTeodora Niculescu
Department of Pathology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
J Immunol 172:5702-6. 2004..Together, these findings are consistent with the role of C5, possibly by forming the membrane attack complex, in limiting OLG apoptosis in EAE, thus promoting remyelination during recovery...
Complement function in mAb-mediated cancer immunotherapyKyra A Gelderman
Department of Pathology L1-Q, Leiden University Medical Center, Postbox 9600, 2300 RC Leiden, The Netherlands
Trends Immunol 25:158-64. 2004
Treatment with an inhibitory monoclonal antibody to mouse factor B protects mice from induction of apoptosis and renal ischemia/reperfusion injuryJoshua 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...
Decay-accelerating factor but not CD59 limits experimental immune-complex glomerulonephritisLihua 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...
Role of complement activation in atherosclerosisRiina Oksjoki
Wihuri Research Institute, Helsinki, Finland
Curr Opin Lipidol 14:477-82. 2003....
Comparison of inflammatory responses after off-pump and on-pump coronary surgery using surface modifying additives circuitJanine 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?..
Complement activation in diabetic ketoacidosis brainsWilliam H Hoffman
Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA
Exp Mol Pathol 80:283-8. 2006....
Complement activation in experimental human malaria infectionMeta 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...
[Membranous glomerulonephritis (membranous nephropathy): Pathogenesis, pathophysiology, and therapy]Teiko Ohashi
Fourth Department of Internal Medicine, Kidney Center, Tokyo Women's Medical University
Nippon Rinsho 64:417-21. 2006
[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....
Terminal complement complex (C5b-9) in children with recurrent hemolytic uremic syndromeFriederike 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...
Pathological study on the relationship between C4d, CD59 and C5b-9 in acute renal allograft rejectionS 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...
[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..CONCLUSION: hDAF displayed on the surface of yeast cells can fold correctly and exhibit activity of complement's inhibition...
Disodium Disuccinate Astaxanthin (Cardax) attenuates complement activation and reduces myocardial injury following ischemia/reperfusionD 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....
The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesionsBianca 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...
The complement system in central nervous system diseasesHorea 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...
Recent advances on the complement system of teleost fishH 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...
Local production of complement proteins in rheumatoid arthritis synoviumElena Neumann
University of Regensburg, Regensburg, Germany
Arthritis Rheum 46:934-45. 2002..CONCLUSION: In summary, local complement production and activation may play an important role in RA, and specific modulation and inhibition of local complement production could be an attractive therapeutic target for RA...
Letter in response to A. Agrawal: 'CRP after 2004'Carmen W van den Berg
Mol Immunol 43:292-3. 2006
The membrane attack pathway of complement drives pathology in passively induced experimental autoimmune myasthenia gravis in miceB 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...
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...
Complement activation during sepsis in humansHeike Schreiber
Dept. of Traumatology, Hand, Plastic, and Reconstructive Surgery, Steinhoevelstr.9, 89075 Ulm, Germany
Adv Exp Med Biol 586:217-26. 2006
Soluble human complement receptor 1 limits ischemic damage in cardiac surgery patients at high risk requiring cardiopulmonary bypassHarold L Lazar
Department of Cardiothoracic Surgery, Boston University School of Medicine and Boston Medical Center, Boston, Mass 02118, USA
Circulation 110:II274-9. 2004....
C5b-9 complement complex in autoimmune demyelination: dual role in neuroinflammation and neuroprotectionHorea Rus
Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
Adv Exp Med Biol 586:139-51. 2006
Retinal synthesis and deposition of complement components induced by ocular hypertensionMarkus 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...
Possible mechanism for medial smooth muscle cell injury in diabetic nephropathy: glycoxidation-mediated local complement activationNoriko 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...
A case of renal sarcoidosis with complement activation via the lectin pathwayShinji 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...
A protein toxin from the sea anemone Phyllodiscus semoni targets the kidney and causes a severe renal injury with predominant glomerular endothelial damageMasashi 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...
Complement activates the c-Jun N-terminal kinase/stress-activated protein kinase in glomerular epithelial cellsHongwei Peng
Department of Medicine, McGill University Health Center, McGill University, Montreal, Quebec, Canada
J Immunol 169:2594-601. 2002..AA may activate the NADPH oxidase, leading to production of reactive oxygen species, which in turn mediate the activation of JNK. The functional role of JNK activation is to limit or protect GECs from complement attack...
Complement and dilated cardiomyopathy: a role of sublytic terminal complement complex-induced tumor necrosis factor-alpha synthesis in cardiac myocytesThomas P Zwaka
Department of Internal Medicine II Cardiology, University of Ulm, Ulm, Germany
Am J Pathol 161:449-57. 2002..We conclude that chronic immunoglobulin-mediated complement activation in the myocardium may contribute in part to the progression of dilated cardiomyopathy via C5b-9-induced TNF-alpha expression in cardiac myocytes...
Complement's participation in acquired immunityClaus Henrik Nielsen
Institute for Inflammation Research, Rigshospitalet, University Hospital Copenhagen, Denmark
J Leukoc Biol 72:249-61. 2002..The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses...
Herpes simplex virus 1 infected neuronal and skin cells differ in their susceptibility to complement attackRiina 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...
Effects of C-reactive protein and pentosan polysulphate on human complement activationAndis 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...
Complement activation alters myocellular sodium homeostasis during polymicrobial sepsisWeiyang Wang
Department of Surgery, Creighton University Medical Center, Omaha, NE 68131, USA
Crit Care Med 30:684-91. 2002....
Crry, but not CD59 and DAF, is indispensable for murine erythrocyte protection in vivo from spontaneous complement attackTakashi 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...
The inhibitory effect of CD46, CD55, and CD59 on complement activation after immunotherapeutic treatment of cervical carcinoma cells with monoclonal antibodies or bispecific monoclonal antibodiesKyra A Gelderman
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Lab Invest 82:483-93. 2002..These results demonstrate that when tumor-associated antigens are expressed in adequate amounts, bispecific mAbs in vivo may be potent immunotherapeutic agents to enhance an inflammatory reaction at the tumor site...
Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathyM 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...
Complement activation in infective endocarditis: correlation with extracardiac manifestations and prognosisI 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...
The membrane attack complex of complement induces caspase activation and apoptosisAlma 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...
Anti-disialoside antibodies kill perisynaptic Schwann cells and damage motor nerve terminals via membrane attack complex in a murine model of neuropathySusan 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...
Intraglomerular synthesis of complement C3 and its activation products in IgA nephropathyK Abe
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1 7 1, Sakamoto, Nagasaki 852 5201, Japan
Nephron 87:231-9. 2001....
Leaked protein and interstitial damage in the kidney: is complement the missing link?N S Sheerin
Department of Nephrology and Transplantation, Guy s Hospital, King s College London, London, UK
Clin Exp Immunol 130:1-3. 2002
Subversion of complement activation at the bacterial surface promotes serum resistance and opsonophagocytosis of Francisella tularensisAbdelhakim 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...
Serum anti-cholesterol antibodies in chronic hepatitis-C patients during IFN-alpha-2b treatmentAdrienn 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...
Association between complement factor H and proteoglycans in early human coronary atherosclerotic lesions: implications for local regulation of complement activationRiina Oksjoki
Wihuri Research Institute, Helsinki, Finland
Arterioscler Thromb Vasc Biol 23:630-6. 2003..Thus, the superficial and the deep layers of the human coronary artery appear to differ in their ability to regulate complement activation...
Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: inhibition of late apoptosis and inflammationBart de Vries
Department of General Surgery, Nutrition and Toxicology Research Institute Maastricht (NUTRIM, Maastricht University, Maastricht, The Netherlands
Transplantation 75:375-82. 2003..Complement inhibition, by preventing C5 activation, abrogates late apoptosis and inflammation, being strongly protective against renal function loss...
A possible role for complement in the pathogenesis of chronic chagasic cardiomyopathyVera Demarchi Aiello
Heart Institute InCor, University of Sao Paulo Medical School, Sao Paulo, Brazil
J Pathol 197:224-9. 2002..It is proposed that the increased MAC deposition found in CCH, but not in DCM or controls, may help to explain the diffuse myocardial fibrosis and inflammation characteristic of the disease...
Comparison of C-reactive protein and terminal complement complex in patients with unstable angina pectoris versus stable angina pectorisHans Martin Hoffmeister
Klinik für Kardiologie und Allgemeine Innere Medizin, Stäedtisches Klinikum Solingen, Solingen, Germany
Am J Cardiol 89:909-12. 2002..This may explain the prognostic value of CRP in acute coronary syndromes (ACS)...
Mechanism of complement activation during extracorporeal blood-biomaterial interaction: effects of heparin coated and uncoated surfacesRuedger 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...
Time course of complement activation and inhibitor expression after ischemic injury of rat myocardiumA 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...
Early complement activation and decreased levels of glycosylphosphatidylinositol-anchored complement inhibitors in human and experimental diabetic retinopathyJing 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...
Marked activation of complement and leukocytes and an increase in the concentrations of soluble endothelial adhesion molecules during cardiopulmonary resuscitation and early reperfusion after cardiac arrest in humansBernd W Böttiger
Department of Anesthesiology, University of Heidelberg, Germany
Crit Care Med 30:2473-80. 2002..We studied different specific markers of these processes during and after cardiopulmonary resuscitation in humans...
Complement activation in chromosome 13 dementias. Similarities with Alzheimer's diseaseAgueda Rostagno
Department of Pathology, School of Medicine, New York University, 550 First Avenue, New York, NY 10016, USA
J Biol Chem 277:49782-90. 2002..The data suggest that the chronic inflammatory response generated by the amyloid peptides in vivo might be a contributing factor for the pathogenesis of FBD and FDD and, in more general terms, to other neurodegenerative conditions...
The use of C3d and C4d immunohistochemistry on formalin-fixed tissue as a diagnostic adjunct in the assessment of inflammatory skin diseaseCynthia M Magro
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York 10065, USA
J Am Acad Dermatol 59:822-33. 2008....
Complement system becomes activated by the classical pathway in intracranial aneurysm wallsRiikka Tulamo
Neurosurgery Research Group, Biomedicum Helsinki, Helsinki, Huch FI 00029, Finland
Lab Invest 90:168-79. 2010..The observed pattern of complement activation may be the consequence of local stress-induced insufficiency of complement regulation in IA walls...
Research Grants
- LUNG INJURY BY OXYGEN METABOLITESPeter Ward; Fiscal Year: 2004..These studies should extend our understanding of the roles of complement activation products in acute lung injury. ..
- MECHANISMS OF COMPLEMENT INDUCED MYOCARDIAL ISCHEMIAGREGORY STAHL; Fiscal Year: 2007..abstract_text> ..
- Complement Activation on Neisseria meningitidisSanjay 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. ..
- MECHANISMS OF COMPLEMENT INDUCED ENDOTHELIAL DYSFUNCTIONGREGORY STAHL; Fiscal Year: 2007..abstract_text> ..
- Anti-Properdin MoAb as a novel therapeutics for arthritisREKHA BANSAL; Fiscal Year: 2007..NovelMed has filed a patent on such inhibitors and additional patents are in preparation. ..
- PATHOGENESIS OF TRANSPLANT-ASSOCIATED ARTERIOSCLEROSISPeter 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 ..
- BIOLOGY OF DECAY ACCELERATING FACTORWenchao 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. ..
- Role of C5a versus C5b-9 in Myocardial Ischemia and Reperfusion InjuryBenjamin Guikema; Fiscal Year: 2007..Drugs currently available may be better used to protect the heart from damage following a heart attack. ..
- Improving Kidney Transplant Outcome with a Novel Complement InhibitorSHELLEY MAVES; Fiscal Year: 2007..Eventually, this therapeutic could also be used to treat acute and chronic humoral rejection, glomerulonephritis and other autoimmune diseases. ..
- Complement Regulatory Proteins and Autoimmune DiseaseWenchao 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. ..
- COMPLEMENT C5 AND C5A RECEPTOR--MOLECULAR GENETICSRICK WETSEL; Fiscal Year: 1999....
- ELECTRON MICROSCOPY OF MYOPATHIESAndrew 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 ..
- Innate Immunity in Gastrointestinal IschemiaMelanie 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. ..
- MECHANISMS OF COMPLEMENT INDUCED ENDOTHELIAL DYSFUNCTIONGREGORY 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. ..
- Targeting complement inhibitors to the human proximal tubuleRichard 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. ..
- DISTAL COMPLEMENT COMPONENTS IN IMMUNE RENAL INJURYWilliam 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...
- PLATELET LEUKOCYTE PHYSIOLOGY IN CARDIOPULMONARY BYPASSBrian 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. ..
