The complement system: History, pathways, cascade and inhibitors

Complement

Walport, M. J. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104053441406 · Cited by 2,927

Anesthesiology

Wiklund, R. A., & Rosenbaum, S. H. (1997) · New England Journal of Medicine · doi:10.1056/nejm199710163371606 · Cited by 2,149

Complement

Walport, M. J. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104123441506 · Cited by 1,481

The Properdin System and Immunity: I. Demonstration and Isolation of a New Serum Protein, Properdin, and Its Role in Immune Phenomena

Pillemer, L., Blum, L., Lepow, I. H., Ross, O. A., Todd, E. W., & Wardlaw, A. C. (1954) · Science · doi:10.1126/science.120.3112.279 · Cited by 938

Complement-dependent Clearance of Apoptotic Cells by Human Macrophages

Mevorach, D., Mascarenhas, J. O., Gershov, D., & Elkon, K. B. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.12.2313 · Cited by 700

CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells.

Davies, A., Simmons, D. L., Hale, G., Harrison, R. A., Tighe, H., Lachmann, P. J., & Waldmann, H. (1989) · The Journal of experimental medicine · doi:10.1084/jem.170.3.637 · Cited by 633

Complement: a unique innate immune sensor for danger signals

GASQUE, P. (2004) · Molecular Immunology · doi:10.1016/j.molimm.2004.06.011 · Cited by 552

Human protectin (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers.

Meri, S., Morgan, B. P., Davies, A., Daniels, R. H., Olavesen, M. G., Waldmann, H., & Lachmann, P. J. (1990) · PubMed Central · Cited by 533

Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidase

Bokisch, V. A., & Müller-Eberhard, H. J. (1970) · Journal of Clinical Investigation · doi:10.1172/jci106462 · Cited by 517

Demonstration of specific C5a receptor on intact human polymorphonuclear leukocytes.

Chenoweth, D. E., & Hugli, T. E. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.8.3943 · Cited by 509

C-Reactive Protein and Complement Are Important Mediators of Tissue Damage in Acute Myocardial Infarction

Griselli, M., Herbert, J., Hutchinson, W. L., Taylor, K. M., Sohail, M., Krausz, T., & Pepys, M. B. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.12.1733 · Cited by 508

Decay-Accelerating Factor: Biochemistry, Molecular Biology, And Function

Lublin, D. (1989) · Annual Review of Immunology · doi:10.1146/annurev.immunol.7.1.35 · Cited by 496

ASSOCIATION OF LOW LEVELS OF MANNAN-BINDING PROTEIN WITH A COMMON DEFECT OF OPSONISATION

Super, M., Lu, J., Thiel, S., Levinsky, R. T., & Turner, M. W. (1989) · The Lancet · doi:10.1016/s0140-6736(89)91849-7 · Cited by 493

Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

Kavanagh, D., Kemp, E. J., Mayland, E., Winney, R. J., Duffield, J. S., Warwick, G., Richards, A., Ward, R., Goodship, J. A., & Goodship, T. H. J. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005010103 · Cited by 475

C5a-induced expression of P-selectin in endothelial cells.

Foreman, K. E., Vaporciyan, A. A., Bonish, B. K., Jones, M. L., Johnson, K. J., Glovsky, M. M., Eddy, S. M., & Ward, P. A. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117430 · Cited by 473

Interaction Between the Coagulation and Complement System

Amara, U., Rittirsch, D., Flierl, M., Bruckner, U., Klos, A., Gebhard, F., Lambris, J. D., & Huber-Lang, M. (2008) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-387-78952-1_6 · Cited by 471

Structure and Function of the Complement Receptors, CR1 (CD35) and CR2 (CD21)

Ahearn, J. M., & Fearon, D. T. (1989) · Advances in Immunology · doi:10.1016/s0065-2776(08)60654-9 · Cited by 448

The Central Role of the Alternative Complement Pathway in Human Disease

Thurman, J. M., & Holers, V. M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.3.1305 · Cited by 432

Complement control protein factor H: The good, the bad, and the inadequate

Ferreira, V. P., Pangburn, M. K., & Cortés, C. (2010) · Molecular Immunology · doi:10.1016/j.molimm.2010.05.007 · Cited by 420

ISOLATION OF ß1F-GLOBULIN FROM HUMAN SERUM AND ITS CHARACTERIZATION AS THE FIFTH COMPONENT OF COMPLEMENT

Nilsson, U. R., & Müller-Eberhard, H. J. (1965) · The Journal of Experimental Medicine · doi:10.1084/jem.122.2.277 · Cited by 412

MASP-3 and Its Association with Distinct Complexes of the Mannan-Binding Lectin Complement Activation Pathway

Dahl, M. R., Thiel, S., Matsushita, M., Fujita, T., Willis, A. C., Christensen, T., Vorup-Jensen, T., & Jensenius, J. C. (2001) · Immunity · doi:10.1016/s1074-7613(01)00161-3 · Cited by 397

The Role of Complement and Its Receptor in the Elimination of Immune Complexes

Epstein, F. H., Schifferli, J. A., Ng, Y. C., & Peters, D. K. (1986) · New England Journal of Medicine · doi:10.1056/nejm198608213150805 · Cited by 396

Complement membrane attack on nucleated cells: resistance, recovery and non-lethal effects

Morgan, B. P. (1989) · Biochemical Journal · doi:10.1042/bj2640001 · Cited by 380

THE PROPERDIN SYSTEM AND IMMUNITY

Pillemer, L., Blum, L., Lepow, I. H., Wurz, L., & Todd, E. W. (1956) · The Journal of Experimental Medicine · doi:10.1084/jem.103.1.1 · Cited by 354

THE ROLE OF THE COMPLEMENT SYSTEM IN ISCHEMIA-REPERFUSION INJURY

Arumugam, T. V., Shiels, I. A., Woodruff, T. M., Granger, D. N., & Taylor, S. M. (2004) · Shock · doi:10.1097/00024382-200405000-00002 · Cited by 327

Isolation and characterization of a mannan-binding protein from rabbit serum

Kozutsumi, Y., Kawasaki, T., & Yamashina, I. (1980) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(80)90836-0 · Cited by 323

Membrane attack by complement: the assembly and biology of terminal complement complexes

Tegla, C. A., Cudrici, C., Patel, S., Trippe, R., Rus, V., Niculescu, F., & Rus, H. (2011) · Immunologic Research · doi:10.1007/s12026-011-8239-5 · Cited by 321

Proteolytic Activities of Two Types of Mannose-Binding Lectin-Associated Serine Protease

Matsushita, M., Thiel, S., Jensenius, J. C., Terai, I., & Fujita, T. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.5.2637 · Cited by 318

Immunology's foundation: the 100-year anniversary of the Nobel Prize to Paul Ehrlich and Elie Metchnikoff

Kaufmann, S. H. E. (2008) · Nature Immunology · doi:10.1038/ni0708-705 · Cited by 292

C5a Induces Tissue Factor Activity on Endothelial Cells

Ikeda, K., Nagasawa, K., Horiuchi, T., Tsuru, T., Nishizaka, H., & Niho, Y. (1997) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1655974 · Cited by 272

Structure and function of the anaphylatoxins

Hugh, T. E. (1984) · Springer Seminars in Immunopathology · doi:10.1007/bf01893020 · Cited by 259

Complement Factor C5a Mediates Renal Ischemia-Reperfusion Injury Independent from Neutrophils

de Vries, B., Köhl, J., Leclercq, W. K. G., Wolfs, T. G. A. M., van Bijnen, A. A. J. H. M., Heeringa, P., & Buurman, W. A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.7.3883 · Cited by 246

Complement deficiency states and associated infections

Skattum, L., van Deuren, M., van der Poll, T., & Truedsson, L. (2011) · Molecular Immunology · doi:10.1016/j.molimm.2011.05.001 · Cited by 240

ANTIMICROBIAL FACTORS OF NORMAL TISSUES AND FLUIDS

Skarnes, R. C., & Watson, D. W. (1957) · Bacteriological Reviews · doi:10.1128/br.21.4.273-294.1957 · Cited by 232

The role of complement in inflammation and adaptive immunity

Barrington, R., Zhang, M., Fischer, M., & Carroll, M. C. (2001) · Immunological Reviews · doi:10.1034/j.1600-065x.2001.1800101.x · Cited by 232

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller, C., Ignatius, A., Gebhard, F., & Huber-Lang, M. (2011) · Molecular Medicine · doi:10.2119/molmed.2010.00149 · Cited by 226

Regulation of the Complement Membrane Attack Pathway

Morgan, B. P. (1999) · Critical Reviews™ in Immunology · doi:10.1615/critrevimmunol.v19.i3.10 · Cited by 222

Isolation and characterization of a mannan-binding protein from rabbit liver

Kawasaki, T., Etoh, R., & Yamashina, I. (1978) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(78)91452-3 · Cited by 216

Generation of C5a by Phagocytic Cells

Huber-Lang, M., Younkin, E. M., Sarma, J. V., Riedemann, N., McGuire, S. R., Lu, K. T., Kunkel, R., Younger, J. G., Zetoune, F. S., & Ward, P. A. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64461-6 · Cited by 212

Collectin 11 (CL-11, CL-K1) Is a MASP-1/3–Associated Plasma Collectin with Microbial-Binding Activity

Hansen, S., Selman, L., Palaniyar, N., Ziegler, K., Brandt, J., Kliem, A., Jonasson, M., Skjoedt, M.-O., Nielsen, O., Hartshorn, K., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002185 · Cited by 204

Ficolins and the lectin complement pathway

Matsushita, M., & Fujita, T. (2001) · Immunological Reviews · doi:10.1034/j.1600-065x.2001.1800107.x · Cited by 203

Distinct Pathways of Mannan-Binding Lectin (MBL)- and C1-Complex Autoactivation Revealed by Reconstitution of MBL with Recombinant MBL-Associated Serine Protease-2

Vorup-Jensen, T., Petersen, S. V., Hansen, A. G., Poulsen, K., Schwaeble, W., Sim, R. B., Reid, K. B. M., Davis, S. J., Thiel, S., & Jensenius, J. C. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.4.2093 · Cited by 202

ISOLATION AND DESCRIPTION OF THE FOURTH COMPONENT OF HUMAN COMPLEMENT

Müller‐Eberhard, H. J., & Biro, C. E. (1963) · The Journal of Experimental Medicine · doi:10.1084/jem.118.3.447 · Cited by 191

Carboxypeptidase N: a pleiotropic regulator of inflammation

Matthews, K. W., Mueller-Ortiz, S. L., & Wetsel, R. A. (2004) · Molecular Immunology · doi:10.1016/j.molimm.2003.10.002 · Cited by 185

C5a-Induced Gene Expression in Human Umbilical Vein Endothelial Cells

Albrecht, E. A., Chinnaiyan, A. M., Varambally, S., Kumar-Sinha, C., Barrette, T. R., Sarma, J. V., & Ward, P. A. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63173-2 · Cited by 178

ROLE OF THE ALTERNATIVE PATHWAY IN THE EARLY COMPLEMENT ACTIVATION FOLLOWING MAJOR TRAUMA

Ganter, M. T., Brohi, K., Cohen, M. J., Shaffer, L. A., Walsh, M. C., Stahl, G. L., & Pittet, J.-F. (2007) · Shock · doi:10.1097/shk.0b013e3180342439 · Cited by 171

Cytolysis of nucleated cells by complement: cell death displays multi-hit characteristics.

Koski, C. L., Ramm, L. E., Hammer, C. H., Mayer, M. M., & Shin, M. L. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.12.3816 · Cited by 165

Biochemistry and Biology of Anaphylatoxins

Hugli, T. E. (1986) · Complement · doi:10.1159/000467889 · Cited by 163

Membrane complement regulatory proteins: insight from animal studies and relevance to human diseases

Miwa, T., & Song, W.-C. (2001) · International Immunopharmacology · doi:10.1016/s1567-5769(00)00043-6 · Cited by 160

Role for the Alternative Complement Pathway in Ischemia/Reperfusion Injury

Stahl, G. L., Xu, Y., Hao, L., Miller, M., Buras, J. A., Fung, M., & Zhao, H. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63839-4 · Cited by 160

Complement-Mediated Ischemia-Reperfusion Injury

Diepenhorst, G. M. P., van Gulik, T. M., & Hack, C. E. (2009) · Annals of Surgery · doi:10.1097/sla.0b013e3181a38f45 · Cited by 159

The Biological Functions of MBL-Associated Serine Proteases (MASPs)

Hajela, K. (2002) · Immunobiology · doi:10.1078/0171-2985-00147 · Cited by 150

Mouse Crry/p65. Characterization of monoclonal antibodies and the tissue distribution of a functional homologue of human MCP and DAF.

Li, B., Sallee, C., Dehoff, M. H., Foley, S. F., Molina, H. D., & Holers, V. M. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.8.4295 · Cited by 141

Complement regulatory proteins in glomerular diseases

Nangaku, M. (1998) · Kidney International · doi:10.1046/j.1523-1755.1998.00130.x · Cited by 133

Complement mediators in ischemia–reperfusion injury

Arumugam, T. V., Magnus, T. U., Woodruff, T. M., Proctor, L. M., Shiels, I. A., & Taylor, S. M. (2006) · Clinica Chimica Acta · doi:10.1016/j.cca.2006.06.010 · Cited by 132

Complement and innate immunity

Song, W.-C., Sarrias, M., & Lambris, J. D. (2000) · Immunopharmacology · doi:10.1016/s0162-3109(00)80303-3 · Cited by 129

CD46 in innate and adaptive immunity: an update

Cardone, J., Friec, G. L., & Kemper, C. (2011) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2011.04400.x · Cited by 104

Complement: Clinical Aspects and Relevance to Disease

Morgan, B. P. (1991) · Cited by 96

Crosstalk between Complement and Toll-like Receptor Activation in Relation to Donor Brain Death and Renal Ischemia-Reperfusion Injury

Damman, J. J., Daha, M. R., van Son, W. J., Leuvenink, H. G. D., Ploeg, R. J., & Seelen, M. A. (2011) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2011.03475.x · Cited by 96

The new face of anaphylatoxins in immune regulation

Zhou, W. (2011) · Immunobiology · doi:10.1016/j.imbio.2011.07.016 · Cited by 94

Biological effects of C1 inhibitor

Davis, A. E. (2004) · Drug News & Perspectives · doi:10.1358/dnp.2004.17.7.863703 · Cited by 93

Complement deficiency and immune complex disease

Davies, K. A., Schifferli, J. A., & Walport, M. J. (1994) · Springer Seminars in Immunopathology · doi:10.1007/bf01837367 · Cited by 92

Complement factor H and the hemolytic uremic syndrome

Atkinson, J. P., & Goodship, T. H. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070664 · Cited by 85

Effect of interferon-γ on complement gene expression in different cell types

Lappin, D. F., Guc, D., Hill, A., McShane, T., & Whaley, K. (1992) · Biochemical Journal · doi:10.1042/bj2810437 · Cited by 83

Activation of the lectin complement pathway by ficolins

Matsushita, M., Endo, Y., Hamasaki, N., & Fujita, T. (2001) · International Immunopharmacology · doi:10.1016/s1567-5769(00)00045-x · Cited by 82

The first component of human complement (C1): Activation and control

Ziccardi, R. J. (1983) · Springer Seminars in Immunopathology · doi:10.1007/bf00205874 · Cited by 80

Complement: Clinical aspects and relevance to disease

Ross, G. D. (1991) · Immunology Today · doi:10.1016/0167-5699(91)90045-u · Cited by 79

The Role of C5b-9 Terminal Complement Complex in Activation of the Cell Cycle and Transcription

Fosbrink, M. D., Niculescu, F. I., & Rus, H. (2004) · Immunologic Research · doi:10.1385/ir:31:1:37 · Cited by 79

Role of complement and perspectives for intervention in ischemia-reperfusion damage

Banz, Y., & Rieben, R. (2011) · Annals of Medicine · doi:10.3109/07853890.2010.535556 · Cited by 75

Structure and function of human plasma carboxypeptidase N, the anaphylatoxin inactivator

Skidgel, R. A., & Erdös, E. G. (2007) · International Immunopharmacology · doi:10.1016/j.intimp.2007.07.014 · Cited by 72

Molecular cloning of rat and mouse membrane cofactor protein (MCP, CD46): preferential expression in testis and close linkage between the mouse Mcp and Cr2 genes on distal chromosome 1

Miwa, T., Nonaka, M. I., Okada, N., Wakana, S., Shiroishi, T., & Okada, H. (1998) · Immunogenetics · doi:10.1007/s002510050447 · Cited by 70

Identification of complement 5a‐like receptor (C5L2) from astrocytes: characterization of anti‐inflammatory properties

Gavrilyuk, V., Kalinin, S., Hilbush, B. S., Middlecamp, A., McGuire, S. O., Pelligrino, D. A., Weinberg, G. L., & Feinstein, D. L. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02942.x · Cited by 69

THE EIGHTH COMPONENT OF HUMAN COMPLEMENT (C8): ISOLATION, CHARACTERIZATION, AND HEMOLYTIC EFFICIENCY

Manni, J. A., & Müller‐Eberhard, H. J. (1969) · The Journal of Experimental Medicine · doi:10.1084/jem.130.5.1145 · Cited by 62

The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury

Fondevila, C., Shen, X., Tsuchihashi, S.-I., Uchida, Y., Freitas, M. C. S., Ke, B., Busuttil, R. W., & Kupiec‐Weglinski, J. W. (2008) · Liver Transplantation · doi:10.1002/lt.21496 · Cited by 59

Intestinal ischemia-reperfusion injury is mediated by the membrane attack complex

Austen, W. G., Kyriakides, C., Favuzza, J., Wang, Y., Kobzik, L., Moore, F. D., & Hechtman, H. B. (1999) · Surgery · doi:10.1016/s0039-6060(99)70175-3 · Cited by 58

SECTION OF BIOLOGY: THE PROPERDIN SYSTEM*

Pillemer, L. (1955) · Transactions of the New York Academy of Sciences · doi:10.1111/j.2164-0947.1955.tb02817.x · Cited by 57

Interferon-induced transcriptional and post-transcriptional modulation of factor H and C4 binding-protein synthesis in human monocytes

Lappin, D. F., & Whaley, K. (1990) · Biochemical Journal · doi:10.1042/bj2710767 · Cited by 49

Transcriptional control of genes for soluble complement cascade regulatory proteins

Fraczek, L., & Martin, B. K. (2010) · Molecular Immunology · doi:10.1016/j.molimm.2010.08.016 · Cited by 37

A Specific Method for Purification of the Second Component of Guinea Pig Complement and a Chemical Evaluation of the One-Hit Theory

Mayer, M. M., Miller, J. A., & Shin, H. S. (1970) · The Journal of Immunology · doi:10.4049/jimmunol.105.2.327 · Cited by 28

The birth of immunology

Tauber, A. I., & Chernyak, L. (1989) · Cellular Immunology · doi:10.1016/0008-8749(89)90043-9 · Cited by 26

Cloning and characterization of the promoter for the human complement factor I (C3b/C4b inactivator) gene

Minta, J. O., Fung, M., Turner, S., Eren, R., Zemach, L., Rits, M., & Goldberger, G. (1998) · Gene · doi:10.1016/s0378-1119(97)00632-x · Cited by 21

Lectin Activity of the Coagulation Factor VIII/von Willebrand Complex

Santizo, F., Zenteno, E., Pina-Canseco, M. D. S., Cruz, P. A. H., Cruz, M. M., Mayoral, L. P.-C., Pérez‐Campos, E., & Martínez-Cruz, R. (2009) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.217.209 · Cited by 5

Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis

Gralinski, L. E., Sheahan, T. P., Morrison, T. E., Menachery, V. D., Jensen, K., Leist, S. R., Whitmore, A., Heise, M. T., & Baric, R. S. (2018) · mBio · doi:10.1128/mbio.01753-18 · Cited by 655

The associations of cerebrospinal fluid ApoE and C1q with Alzheimer's disease biomarkers

Lin, Y.-J., Liu, Y., Sheng, Z.-H., Fu, Y., Ma, L.-Z., Zhang, Z.-H., Wang, L.-Y., Huang, L.-Y., Liu, M., Wang, Z.-T., et al. (2025) · Journal of Alzheimer’s Disease · doi:10.1177/13872877251320419 · Cited by 3