C5a anaphylatoxin and its role in critical illness-induced organ dysfunction
Open accessAbstract
Critical illness is an aetiologically and clinically heterogeneous syndrome that is characterised by organ failure and immune dysfunction. Mortality in critically ill patients is driven by inflammation‐associated organ damage and a profound vulnerability to nosocomial infection. Both factors are influenced by the activated complement protein C5a, released by unbridled activation of the complement system during critical illness. C5a exerts deleterious effects on organ systems directly and suppresses antimicrobial functions of key immune cells. Whilst several recent reports have added key knowledge of the cellular signalling pathways triggered by C5a, there remain a number of areas that are incompletely understood and therapeutic opportunities are still being evaluated. In this review, we summarise the cellular basis for C5a‐induced vulnerability to nosocomial infection and organ dysfunction. We focus on cells of the innate immune system, highlighting the major areas in need of further research and potential avenues for targeted therapies.
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C5a has well-known pro-inflammatory functions mediated through its C5aR receptors and activation of the NLRP3 inflammasome.
“While it has well-known pro-inflammatory functions mediated through its C5aR receptors and activation of the NLRP3 inflammasome (as previously reviewed [185,186])”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [185]
Cites
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221 · see citing works
DAMPs, PAMPs and alarmins: all we need to know about danger
Bianchi, M. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0306164 · Cited by 2,794 · see citing works
Zerbino, D. R., Achuthan, P., Akanni, W., Amode, M. R., Barrell, D., Bhai, J., Billis, K., Cummins, C., Gall, A., Girón, C. G., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gkx1098 · Cited by 2,605 · see citing works
The immunopathology of sepsis and potential therapeutic targets
van der Poll, T., van de Veerdonk, F. L., Scicluna, B. P., & Netea, M. G. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.36 · Cited by 1,957 · see citing works
The emerging mechanisms of isoform-specific PI3K signalling
Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., & Bilanges, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2882 · Cited by 1,767 · see citing works
Transduction of Receptor Signals by ß-Arrestins
Lefkowitz, R. J., & Shenoy, S. K. (2005) · Science · doi:10.1126/science.1109237 · Cited by 1,729 · see citing works
Hotchkiss, R. S., Moldawer, L. L., Opal, S. M., Reinhart, K., Turnbull, I. R., & Vincent, J. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.45 · Cited by 1,722 · see citing works
The Complement Inhibitor Eculizumab in Paroxysmal Nocturnal Hemoglobinuria
Hillmen, P., Young, N. S., Schubert, J. E. A., Brodsky, R. A., Socié, G., Muus, P., Röth, A., Szer, J., Elebute, M. O., Nakamura, R., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061648 · Cited by 1,304 · see citing works
β-Arrestin: a Protein that Regulates β-adrenergic Receptor Function
Lohse, M. J., Benovic, J., Codina, J., Caron, M. G., & Lefkowitz, R. J. (1990) · Science · doi:10.1126/science.2163110 · Cited by 1,222 · see citing works
Harmful molecular mechanisms in sepsis
Rittirsch, D., Flierl, M. A., & Ward, P. A. (2008) · Nature reviews. Immunology · doi:10.1038/nri2402 · Cited by 1,199 · see citing works
Generation of C5a in the absence of C3: a new complement activation pathway
Huber-Lang, M. S., Sarma, J. V., Zetoune, F. S., Rittirsch, D., Neff, T. A., McGuire, S. R., Lambris, J. D., Warner, R. L., Flierl, M. A., Hoesel, L. M., et al. (2006) · Nature Medicine · doi:10.1038/nm1419 · Cited by 976 · see citing works
The systemic immune response to trauma: an overview of pathophysiology and treatment
Lord, J. M., Midwinter, M. J., Chen, Y., Belli, A., Brohi, K., Kovacs, E. J., Koenderman, L., Kubes, P., & Lilford, R. J. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60687-5 · Cited by 865 · see citing works
Novel strategies for the treatment of sepsis
Riedemann, N. C., Guo, R., & Ward, P. A. (2003) · Nature Medicine · doi:10.1038/nm0503-517 · Cited by 774 · see citing works
Goldstein, I. M., Roos, D., Kaplan, H. B., & Weissmann, G. (1975) · Journal of Clinical Investigation · doi:10.1172/jci108191 · Cited by 746 · see citing works
Biased signalling: from simple switches to allosteric microprocessors
Smith, J. S., Lefkowitz, R. J., & Rajagopal, S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.229 · Cited by 746 · see citing works
The chemotactic receptor for human C5a anaphylatoxin
Gerard, N. P., & Gerard, C. J. (1991) · Nature · doi:10.1038/349614a0 · Cited by 662 · see citing works
Neutrophils in development of multiple organ failure in sepsis
Brown, K., Brain, S. D., Pearson, J. D., Edgeworth, J. D., Sm, L., & Treacher, D. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69005-3 · Cited by 652 · see citing works
Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis
Jayne, D. R. W., Bruchfeld, A. N., Harper, L., Schaier, M., Venning, M. C., Hamilton, P., Burst, V. R., Grundmann, F., Jadoul, M. Y., Szombati, I., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016111179 · Cited by 608 · see citing works
Innate immune responses to trauma
Huber-Lang, M. S., Lambris, J. D., & Ward, P. A. (2018) · Nature Immunology · doi:10.1038/s41590-018-0064-8 · Cited by 604 · see citing works
Complement in disease: a defence system turning offensive
Ricklin, D., Reis, E. S., & Lambris, J. D. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.70 · Cited by 558 · see citing works
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 · see citing works
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 510 · see citing works
Novel mechanisms and functions of complement
Hajishengallis, G., Reis, E. S., Mastellos, D. C., Ricklin, D., & Lambris, J. D. (2017) · Nature Immunology · doi:10.1038/ni.3858 · Cited by 484 · see citing works
Interaction Between the Coagulation and Complement System
Amara, U., Rittirsch, D., Flierl, M. A., Brückner, U. B., Klos, A., Gebhard, F. T., Lambris, J. D., & Huber-Lang, M. S. (2008) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-78952-1_6 · Cited by 474 · see citing works
Cochrane, C. G., & Müller‐Eberhard, H. J. (1968) · The Journal of Experimental Medicine · doi:10.1084/jem.127.2.371 · Cited by 462 · see citing works
Mollnes, T. E., Brekke, O., Fung, M. S. C., Fure, H., Christiansen, D., Bergseth, G., Videm, V., Lappegård, K. T., Köhl, J., & Lambris, J. D. (2002) · PubMed · doi:10.1182/blood.v100.5.1869.h81702001869_1869_1877 · Cited by 455 · see citing works
The dark side of C5a in sepsis
Ward, P. A. (2004) · Nature reviews. Immunology · doi:10.1038/nri1269 · Cited by 420 · see citing works
Protective effects of C5a blockade in sepsis
Czermak, B. J., Sarma, V. J., Pierson, C. L., Warner, R. L., Huber-Lang, M. S., Bless, N. M., Schmal, H., Friedl, H. P., & Ward, P. A. (1999) · Nature Medicine · doi:10.1038/10512 · Cited by 399 · see citing works
Platelet activation leads to activation and propagation of the complement system
Conde, I. D., Crúz, M. A., Zhang, H., López, J. A., & Afshar‐Kharghan, V. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041497 · Cited by 397 · see citing works
Functional roles for C5a receptors in sepsis
Rittirsch, D., Flierl, M. A., Nadeau, B. A., Day, D. E., Huber-Lang, M. S., Mackay, C. R., Zetoune, F. S., Gerard, N. P., Cianflone, K., Köhl, J., et al. (2008) · Nature Medicine · doi:10.1038/nm1753 · Cited by 386 · see citing works
van Gils, J. M., Zwaginga, J. J., & Hordijk, P. L. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0708400 · Cited by 298 · see citing works
The role of neutrophils in immune dysfunction during severe inflammation
Leliefeld, P. H. C., Wessels, C. M., Leenen, L. P. H., Koenderman, L., & Pillay, J. (2016) · Critical Care · doi:10.1186/s13054-016-1250-4 · Cited by 298 · see citing works
Wide-field choroidal thickness profile in healthy eyes
Rasheed, M. A., Singh, S. R., Invernizzi, A., Cagini, C., Goud, A., Sahoo, N. K., Cozzi, M., Lupidi, M., & Chhablani, J. K. (2018) · Scientific Reports · doi:10.1038/s41598-018-35640-9 · Cited by 288 · see citing works
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 · see citing works
Gendron, T. F., Chew, J., Stankowski, J. N., Hayes, L. R., Zhang, Y.-J., Prudencio, M., Carlomagno, Y., Daughrity, L. M., Jansen-West, K., Perkerson, E. A., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aai7866 · Cited by 265 · see citing works
Biological effects of the human complement fragments C5a and C5ades Arg on neutrophil function
Webster, R. O., Hong, S. R., Johnston, R. B., & Henson, P. M. (1980) · Immunopharmacology · doi:10.1016/0162-3109(80)90050-8 · Cited by 261 · see citing works
C5L2, a Nonsignaling C5A Binding Protein
Okinaga, S., Slattery, D. M., Humbles, A. A., Zsengellér, Z. K., Morteau, O., Kinrade, M. B., Brodbeck, R. M., Krause, J. E., Choe, H.-R., Gerard, N. P., et al. (2003) · Biochemistry · doi:10.1021/bi034489v · Cited by 261 · see citing works
Fernández, H. N., & Hugli, T. E. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38013-4 · Cited by 251 · see citing works
Subramaniam, S., Jurk, K., Hobohm, L., Jäckel, S., Saffarzadeh, M., Schwierczek, K., Wenzel, P., Länger, F. P., Reinhardt, C., & Ruf, W. (2017) · Blood · doi:10.1182/blood-2016-11-749879 · Cited by 251 · see citing works
The C5a Receptor (C5aR) C5L2 Is a Modulator of C5aR-mediated Signal Transduction
Bamberg, C. E., Mackay, C. R., Lee, H., Zahra, D., Jackson, J., Lim, Y. S., Whitfeld, P. L., Craig, S., Corsini, E. M., Lu, B., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.092106 · Cited by 249 · see citing works
Cain, S. A., & Monk, P. N. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c100714200 · Cited by 245 · see citing works
Complement alternative pathway acts as a positive feedback amplification of neutrophil activation
Camous, L., Roumenina, L., Bigot, S., Brachemi, S., Frémeaux-Bacchi, V., Lesavre, P., & Halbwachs-Mecarelli, L. (2011) · Blood · doi:10.1182/blood-2010-05-283564 · Cited by 244 · see citing works
The Potential Pathogenic Role of Complement in Dengue Hemorrhagic Shock Syndrome
Bokisch, V. A., Top, F. H., Russell, P. K., Dixon, F. J., & Müller‐Eberhard, H. J. (1973) · New England Journal of Medicine · doi:10.1056/nejm197311082891902 · Cited by 240 · see citing works
Siciliano, S. J., Rollins, T. E., DeMartino, J. A., Konteatis, Z. D., Malkowitz, L., Riper, G. V., Bondy, S. S., Rosen, H., & Springer, M. S. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.4.1214 · Cited by 233 · see citing works
Role of C5a in Multiorgan Failure During Sepsis
Huber-Lang, M. S., Sarma, V. J., Lu, K. T., McGuire, S. R., Padgaonkar, V. A., Guo, R., Younkin, E. M., Kunkel, R. G., Ding, J., Erickson, R. W., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.2.1193 · Cited by 224 · see citing works
Inactivation of C3a and C5a Octapeptides by Carboxypeptidase R and Carboxypeptidase N
Campbell, W. D., Lazoura, E., Okada, N., & Okada, H. (2002) · Microbiology and Immunology · doi:10.1111/j.1348-0421.2002.tb02669.x · Cited by 224 · see citing works
Rinder, C. S., Rinder, H. M., Smith, B. R., Fitch, J. C. K., Smith, M. J., Tracey, J. B., Matis, L. A., Squinto, S. P., & Rollins, S. A. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118195 · Cited by 213 · see citing works
Generation of C5a by Phagocytic Cells
Huber-Lang, M. S., Younkin, E. M., Sarma, J. V., Riedemann, N. C., McGuire, S. R., Lu, K. T., Kunkel, R., Younger, J. G., Zetoune, F. S., & Ward, P. A. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64461-6 · Cited by 212 · see citing works
An Anti-inflammatory Function for the Complement Anaphylatoxin C5a-binding Protein, C5L2
Gerard, N. P., Lu, B., Liu, P., Craig, S., Fujiwara, Y., Okinaga, S., & Gerard, C. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500287200 · Cited by 201 · see citing works
Complement-Induced Impairment of Innate Immunity During Sepsis
Huber-Lang, M. S., Younkin, E. M., Sarma, J. V., McGuire, S. R., Lu, K. T., Guo, R. F., Padgaonkar, V. A., Curnutte, J. T., Erickson, R. W., & Ward, P. A. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.6.3223 · Cited by 200 · see citing works
Ohno, M., Hirata, T., Enomoto, M., Araki, T., Ishimaru, H., & Takahashi, T. A. (2000) · Molecular Immunology · doi:10.1016/s0161-5890(00)00067-5 · Cited by 195 · see citing works
Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy.
Matsuda, N., & Hattori, Y. (2006) · Journal of Pharmacological Sciences · doi:10.1254/jphs.crj06010x · Cited by 191 · see citing works
Suire, S., Condliffe, A. M., Ferguson, G., Ellson, C. D., Guillou, H., Davidson, K., Welch, H. C. E., Coadwell, J., Turner, M., Chilvers, E. R., et al. (2006) · Nature Cell Biology · doi:10.1038/ncb1494 · Cited by 168 · see citing works
Self-citationProtection of innate immunity by C5aR antagonist in septic mice
Huber-Lang, M. S., Riedemann, N. C., Sarma, J. V., Younkin, E. M., McGuire, S. R., Laudes, I. J., Lu, K. T., Guo, R., Neff, T. A., Padgaonkar, V. A., et al. (2002) · The FASEB Journal · doi:10.1096/fj.02-0209com · Cited by 161 · see citing works
The Harmful Role of C5a on Innate Immunity in Sepsis
Ward, P. A. (2010) · Journal of Innate Immunity · doi:10.1159/000317194 · Cited by 159 · see citing works
Infections associated with the use of eculizumab: recommendations for prevention and prophylaxis
Benamu, E., & Montoya, J. G. (2016) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0000000000000279 · Cited by 154 · see citing works
An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction
Niederbichler, A. D., Hoesel, L. M., Westfall, M. V., Gao, H., Ipaktchi, K. R., Sun, L., Zetoune, F. S., Su, G. L., Arbabi, S., Sarma, J. V., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051207 · Cited by 147 · see citing works
Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin
Foley, J. H., Walton, B. L., Aleman, M. M., O'Byrne, A. M., Lei, V. J., Harrasser, M., Foley, K., Wolberg, A. S., & Conway, E. M. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.02.011 · Cited by 144 · see citing works
Receptors for complement C5a. The importance of C5aR and the enigmatic role of C5L2
Lee, H., Whitfeld, P. L., & Mackay, C. R. (2008) · Immunology and Cell Biology · doi:10.1038/sj.icb.7100166 · Cited by 141 · see citing works
Human C5a and C5a analogs as probes of the neutrophil C5a receptor
Chenoweth, D. E., & Hugli, T. E. (1980) · Molecular Immunology · doi:10.1016/0161-5890(80)90067-x · Cited by 133 · see citing works
The p110δ isoform of PI 3‐kinase negatively controls RhoA and PTEN
Papakonstanti, E. A., Ridley, A. J., & Vanhaesebroeck, B. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601763 · Cited by 130 · see citing works
Solomkin, J. S., Jenkins, M. K., Nelson, R. D., Chenoweth, D. E., & Simmons, R. L. (1981) · PubMed · Cited by 129 · see citing works
Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study
Morris, A. C., Datta, D., Shankar‐Hari, M., Stephen, J., Weir, C. J., Rennie, J., Antonelli, J., Bateman, A. P., Warner, N. L., Judge, K. W., et al. (2018) · Intensive Care Medicine · doi:10.1007/s00134-018-5247-0 · Cited by 125 · see citing works
Mapping of the C5a receptor signal transduction network in human neutrophils.
Buhl, A. M., Avdi, N. J., Worthen, G. S., & Johnson, G. L. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.9190 · Cited by 123 · see citing works
C5a Mediates Peripheral Blood Neutrophil Dysfunction in Critically Ill Patients
Morris, A. C., Kefala, K., Wilkinson, T. S., Dhaliwal, K., Farrell, L., Walsh, T. S., MacKenzie, S. J., Reid, H., Davidson, D. J., Haslett, C., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200812-1928oc · Cited by 123 · see citing works
C5a delays apoptosis of human neutrophils by a phosphatidylinositol 3-kinase-signaling pathway
Perianayagam, M. C., Balakrishnan, V. S., King, A. J., Pereira, B. J. G., & Jaber, B. L. (2002) · Kidney International · doi:10.1046/j.1523-1755.2002.00139.x · Cited by 121 · see citing works
Regulation by C5a of Neutrophil Activation during Sepsis
Riedemann, N. C., Guo, R., Bernacki, K. D., Reuben, J. S., Laudes, I. J., Neff, T. A., Gao, H., Speyer, C. L., Sarma, V. J., Zetoune, F. S., et al. (2003) · Immunity · doi:10.1016/s1074-7613(03)00206-1 · Cited by 121 · see citing works
Complement‐induced activation of the cardiac NLRP3 inflammasome in sepsis
Kalbitz, M., Fattahi, F., Grailer, J. J., Jajou, L., Malan, E. A., Zetoune, F. S., Huber-Lang, M. S., Russell, M. W. W., & Ward, P. A. (2016) · The FASEB Journal · doi:10.1096/fj.201600728r · Cited by 120 · see citing works
Brekke, O., Christiansen, D., Fure, H., Fung, M. S. C., & Mollnes, T. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0806538 · Cited by 118 · see citing works
Morris, A. C., Brittan, M., Wilkinson, T. S., McAuley, D. F., Antonelli, J., McCulloch, C., Barr, L. C., McDonald, N. A., Dhaliwal, K., Jones, R. O., et al. (2011) · Blood · doi:10.1182/blood-2010-08-304667 · Cited by 113 · see citing works
Zuiderweg, E. R. P., Nettesheim, D. G., Mollison, K. W., & Carter, G. W. (1989) · Biochemistry · doi:10.1021/bi00427a025 · Cited by 100 · see citing works
Changes and Regulation of the C5a Receptor on Neutrophils during Septic Shock in Humans
Unnewehr, H., Rittirsch, D., Sarma, J. V., Zetoune, F. S., Flierl, M. A., Perl, M., Denk, S., Weiß, M., Schneider, M. E., Monk, P. N., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1200534 · Cited by 98 · see citing works
Biased G Protein–Coupled Receptor Signaling
Wisler, J. W., Rockman, H. A., & Lefkowitz, R. J. (2018) · Circulation · doi:10.1161/circulationaha.117.028194 · Cited by 96 · see citing works
Hoehlig, K., Maasch, C., Shushakova, N., Buchner, K., Huber-Lang, M. S., Purschke, W. G., Vater, A., & Klußmann, S. (2013) · Molecular Therapy · doi:10.1038/mt.2013.178 · Cited by 93 · see citing works
Edwards, A. T. (1946) · Thorax · doi:10.1136/thx.1.1.1 · Cited by 89 · see citing works
Complement C5a‐Induced Changes in Neutrophil Morphology During Inflammation
Denk, S., Taylor, R. P., Wiegner, R., Cook, E. M., Lindorfer, M. A., Pfeiffer, K., Paschke, S., Eiseler, T., Weiss, M., Barth, E., et al. (2017) · Scandinavian Journal of Immunology · doi:10.1111/sji.12580 · Cited by 89 · see citing works
Complement C5a in the Sepsis Syndrome — Too Much of a Good Thing?
Gerard, C. J. (2003) · New England Journal of Medicine · doi:10.1056/nejmcibr022995 · Cited by 88 · see citing works
Combined dysfunctions of immune cells predict nosocomial infection in critically ill patients
Morris, A. C., Anderson, N., Brittan, M., Wilkinson, T. S., McAuley, D. F., Antonelli, J., McCulloch, C., Barr, L. C., Dhaliwal, K., Jones, R. O., et al. (2013) · British Journal of Anaesthesia · doi:10.1093/bja/aet205 · Cited by 87 · see citing works
Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2
Mazaki, Y., Hashimoto, S., Tsujimura, T., Morishige, M., Hashimoto, A., Aritake, K., Yamada, A., Nam, J.-M., Kiyonari, H., Nakao, K., et al. (2006) · Nature Immunology · doi:10.1038/ni1349 · Cited by 86 · see citing works
Plasma clearance of the human C5a anaphylatoxin by binding to leucocyte C5a receptors.
Oppermann, M., & Götze, O. (1994) · PubMed · Cited by 83 · see citing works
Proudfoot, A. G., Bayliffe, A. I., O’Kane, C. M., Wright, T. J., Serone, A., Bareille, P. J., Brown, V., Hamid, U. I., Chen, Y., Wilson, R., et al. (2018) · Thorax · doi:10.1136/thoraxjnl-2017-210305 · Cited by 81 · see citing works
Self-citationChanges in the Novel Orphan, C5a Receptor (C5L2), during Experimental Sepsis and Sepsis in Humans
Huber-Lang, M. S., Sarma, J. V., Rittirsch, D., Schreiber, H. A., Weiss, M., Flierl, M. A., Younkin, E. M., Schneider, M., Suger-Wiedeck, H., Gebhard, F. T., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.2.1104 · Cited by 79 · see citing works
Seow, V., Lim, J., Iyer, A., Suen, J. Y., Ariffin, J. K., Hohenhaus, D. M., Sweet, M. J., & Fairlie, D. P. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301355 · Cited by 79 · see citing works
Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signalling
Croker, D. E., Monk, P. N., Halai, R., Kaeslin, G., Schofield, Z., Wu, M. C. L., Clark, R. J., Blaskovich, M. A. T., Morikis, D., Floudas, C. A., et al. (2016) · Immunology and Cell Biology · doi:10.1038/icb.2016.43 · Cited by 78 · see citing works
GPCR activation of Ras and PI3Kγ in neutrophils depends on PLCβ2/β3 and the RasGEF RasGRP4
Suire, S., Lécureuil, C., Anderson, K. E., Damoulakis, G., Niewczas, I., Davidson, K., Guillou, H., Pan, D., Clark, J., Hawkins, P. T., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.167 · Cited by 77 · see citing works
The intensive care medicine research agenda on septic shock
Perner, A., Gordon, A. C., Angus, D. C., Lamontagne, F., Machado, F. R., Russell, J. A., Timsit, J., Marshall, J. C., Myburgh, J., Shankar‐Hari, M., et al. (2017) · Intensive Care Medicine · doi:10.1007/s00134-017-4821-1 · Cited by 75 · see citing works
C5a alters blood–brain barrier integrity in a human in vitro model of systemic lupus erythematosus
Mahajan, S. D., Parikh, N. U., Woodruff, T. M., Jarvis, J. N., Lopez, M., Hennon, T., Cunningham, P. N., Quigg, R. J., Schwartz, S. A., & Alexander, J. J. (2015) · Immunology · doi:10.1111/imm.12489 · Cited by 74 · see citing works
Webster, R. O., Larsen, G. L., & Henson, P. M. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110716 · Cited by 74 · see citing works
Perianayagam, M. C., Balakrishnan, V. S., Pereira, B. J. G., & Jaber, B. L. (2004) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2004.01273.x · Cited by 73 · see citing works
The Controversial C5a Receptor C5aR2: Its Role in Health and Disease
Zhang, T., Garstka, M. A., & Li, K. (2017) · Journal of Immunology Research · doi:10.1155/2017/8193932 · Cited by 72 · see citing works
Morris, A. C., Wilson, J., & Shankar‐Hari, M. (2017) · Critical Care Clinics · doi:10.1016/j.ccc.2017.08.002 · Cited by 72 · see citing works
Croker, D. E., Halai, R., Kaeslin, G., Wende, E., Fehlhaber, B., Klos, A., Monk, P. N., & Cooper, M. A. (2014) · Immunology and Cell Biology · doi:10.1038/icb.2014.32 · Cited by 70 · see citing works
van den Berg, C. W., Tambourgi, D. V., Clark, H. W., Hoong, S. J., Spiller, O. B., & McGreal, E. P. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301920 · Cited by 70 · see citing works
Neutrophil macroaggregates promote widespread pulmonary thrombosis after gut ischemia
Yuan, Y., Alwis, I. D., Wu, M. C. L., Kaplan, Z., Ashworth, K. J., Bark, D. L., Pham, A., McFadyen, J. D., Schoenwaelder, S. M., Josefsson, E. C., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aam5861 · Cited by 70 · see citing works
Grégoire, M., Tadié, J., Uhel, F., Gacouin, A., Piau, C., Bone, N. B., Tulzo, Y. L., Abraham, E. H., Tarte, K., & Zmijewski, J. W. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.5hi0316-128rr · Cited by 69 · see citing works
Johswich, K. O., Martin, M., Thalmann, J., Rheinheimer, C., Monk, P. N., & Klos, A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m609734200 · Cited by 67 · see citing works
Examining coagulation-complement crosstalk: complement activation and thrombosis
Foley, J. H. (2016) · Thrombosis Research · doi:10.1016/s0049-3848(16)30365-6 · Cited by 63 · see citing works
Denk, S., Neher, M. D., Messerer, D. A. C., Wiegner, R., Nilsson, B., Rittirsch, D., Nilsson‐Ekdahl, K., Weckbach, S., Ignatius, A. A., Kalbitz, M., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700393 · Cited by 61 · see citing works
Jain, U., Woodruff, T. M., & Stadnyk, A. W. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02183.x · Cited by 60 · see citing works
Structure-Function Relationships of Human C5a and C5aR
Huber-Lang, M. S., Sarma, J. V., McGuire, S. R., Lu, K. T., Padgaonkar, V. A., Younkin, E. M., Guo, R. F., Weber, C. H., Zuiderweg, E. R. P., Zetoune, F. S., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.12.6115 · Cited by 60 · see citing works
Complement‐induced activation of MAPKs and Akt during sepsis: role in cardiac dysfunction
Fattahi, F., Kalbitz, M., Malan, E. A., Abe, E. A., Jajou, L., Huber-Lang, M. S., Bosmann, M., Russell, M. W. W., Zetoune, F. S., & Ward, P. A. (2017) · The FASEB Journal · doi:10.1096/fj.201700140r · Cited by 55 · see citing works
C5a-Stimulated Recruitment of β-Arrestin2 to the Nonsignaling 7-Transmembrane Decoy Receptor C5L2
van Lith, L. H. C. J., Oosterom, J., van Elsas, A., & Zaman, G. J. R. (2009) · SLAS DISCOVERY · doi:10.1177/1087057109341407 · Cited by 53 · see citing works
Complement and sepsis-induced heart dysfunction
Fattahi, F., & Ward, P. A. (2016) · Molecular Immunology · doi:10.1016/j.molimm.2016.11.012 · Cited by 52 · see citing works
Phagocytosing neutrophils down-regulate the expression of chemokine receptors CXCR1 and CXCR2
Doroshenko, T., Chaly, Y., Savitski, V. P., Maslakova, O. V., Portyanko, A., Gorudko, I. V., & Voitenok, N. N. (2002) · Blood · doi:10.1182/blood.100.7.2668 · Cited by 48 · see citing works
Mehta, Y. B., & Kochhar, G. (2017) · Journal of Cardiac Critical Care TSS · doi:10.1055/s-0037-1604204 · Cited by 48 · see citing works
C5a induces caspase‐dependent apoptosis in brain vascular endothelial cells in experimental lupus
Mahajan, S. D., Tutino, V. M., Redae, Y. Z., Meng, H., Siddiqui, A. H., Woodruff, T. M., Jarvis, J. N., Hennon, T., Schwartz, S. A., Quigg, R. J., et al. (2016) · Immunology · doi:10.1111/imm.12619 · Cited by 47 · see citing works
Looking back on the alternative complement pathway
Lachmann, P. J. (2018) · Immunobiology · doi:10.1016/j.imbio.2018.02.001 · Cited by 45 · see citing works
C5a- and ASP-mediated C5L2 activation, endocytosis and recycling are lost in S323I-C5L2 mutation
Cui, W., Simaan, M., Laporte, S. A., Lodge, R., & Cianflone, K. (2009) · Molecular Immunology · doi:10.1016/j.molimm.2009.06.007 · Cited by 42 · see citing works
Landsem, A., Fure, H., Christiansen, D., Nielsen, E. W., Østerud, B., Mollnes, T. E., & Brekke, O. (2015) · Clinical & Experimental Immunology · doi:10.1111/cei.12663 · Cited by 42 · see citing works
Combined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsis
Skjeflo, E. W., Sagatun, C., Dybwik, K., Aam, S., Urving, S. H., Nunn, M. A., Fure, H., Lau, C., Brekke, O., Huber-Lang, M. S., et al. (2015) · Critical Care · doi:10.1186/s13054-015-1129-9 · Cited by 42 · see citing works
Human C5a-related synthetic peptides as neutrophil chemotactic factors
Chenoweth, D. E., Erickson, B. W., & Hugli, T. E. (1979) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(79)90856-8 · Cited by 36 · see citing works
Colley, C. S., Popovic, B., Sridharan, S., Debreczeni, J. E., Hargeaves, D., Fung, M. S. C., An, L., Edwards, B. M., Arnold, J., England, E., et al. (2017) · mAbs · doi:10.1080/19420862.2017.1384892 · Cited by 34 · see citing works
Scott, J., Harris, G. J., Pinder, E. M., Macfarlane, J., Hellyer, T. P., Rostron, A., Morris, A. C., THICKETT, D. R., Perkins, G. D., McAuley, D. F., et al. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.07.036 · Cited by 30 · see citing works
Staphylococcus aureus‐induced complement activation promotes tissue factor‐mediated coagulation
Skjeflo, E. W., Christiansen, D., Fure, H., Ludviksen, J. K., Woodruff, T. M., Espevik, T., Nielsen, E. W., Brekke, O., & Mollnes, T. E. (2018) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13979 · Cited by 30 · see citing works
Øvstebø, R., Hellum, M., Aass, H. C. D., Trøseid, A. M. S., Brandtzaeg, P., Mollnes, T. E., & Henriksson, C. E. (2013) · Innate Immunity · doi:10.1177/1753425913502099 · Cited by 28 · see citing works
Modeling Molecular Mechanisms of Binding of the Anaphylatoxin C5a to the C5a Receptor
Nikiforovich, G. V., Marshall, G. R., & Baranski, T. (2008) · Biochemistry · doi:10.1021/bi702321a · Cited by 27 · see citing works
Hagemann, I. S., Miller, D. L., Klco, J. M., Nikiforovich, G. V., & Baranski, T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709467200 · Cited by 25 · see citing works
Sahoo, A. R., Mishra, R., & Rana, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-21290-4 · Cited by 22 · see citing works
DeMaster, E., Schnitzler, N., Cheng, Q., & Cleary, P. P. (2002) · Infection and Immunity · doi:10.1128/iai.70.1.350-359.2002 · Cited by 21 · see citing works
del Balzo, U., Sakuma, I., & Levi, R. (1990) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)12439-7 · Cited by 20 · see citing works
Hagemann, I. S., Narzinski, K., Floyd, D. H., & Baranski, T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607686200 · Cited by 18 · see citing works
Myeloid-derived Suppressor Cells in Sepsis
van der Poll, T. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201701-0046ed · Cited by 13 · see citing works
Helical conformation at the carboxy-terminal portion of human C3a is required for full activity
Hoeprich, P. D., & Hugli, T. E. (1986) · Biochemistry · doi:10.1021/bi00356a017 · Cited by 12 · see citing works
Initial Characterization of the Human Polymorphonuclear Leukocyte (PMN) C5a Receptor
Chenoweth, D. E., & Hugli, T. E. (1978) · The Journal of Immunology · doi:10.4049/jimmunol.120.5.1768.c · Cited by 11 · see citing works
Dobos, G., Andre, M., Böhler, J., Norgauer, J., Lubrich-Birkner, I., Hb, S., & Schollmeyer, P. J. (1993) · PubMed · Cited by 9 · see citing works
Morris, A. C., Datta, D., Shankar‐Hari, M., Weir, C. J., Rennie, J., Antonelli, J., Rossi, A. G., Warner, N. L., Keenan, J., Wang, A., et al. (2016) · BMJ Open · doi:10.1136/bmjopen-2016-011326 · Cited by 8 · see citing works
Innate immune responses of exfoliated epithelial cells
Srinivasan, M., Swaminathan, V., Negrini, T. D. C., & Arthur, R. A. (2013) · Acervo Digital da Universidade Estadual Paulista (Universidade Estadual Paulista) · Cited by 6 · see citing works
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Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics
Garred, P., Tenner, A. J., & Mollnes, T. E. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000072 · Cited by 215 · see citing works
Dowey, R., Iqbal, A., Heller, S. R., Sabroe, I., & Prince, L. R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.678771 · Cited by 144 · see citing works
Immune modulation after traumatic brain injury
Bouras, M., Asehnoune, K., & Roquilly, A. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.995044 · Cited by 96 · see citing works
Coagulation and complement: Key innate defense participants in a seamless web
Pryzdial, E. L. G., Leatherdale, A., & Conway, E. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.918775 · Cited by 85 · see citing works
Yu, S., Wang, D., Huang, L., Zhang, Y., Luo, R., Adah, D., Tang, Y., Zhao, K., & Lü, B. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006508 · Cited by 69 · see citing works
The anaphylatoxin C5a: Structure, function, signaling, physiology, disease, and therapeutics
Ghosh, M., & Rana, S. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110081 · Cited by 64 · see citing works
Reyes, L. F., Morris, A. C., Serrano-Mayorga, C. C., Derde, L. P. G., Dickson, R. P., & Martín‐Loeches, I. (2025) · The Lancet · doi:10.1016/s0140-6736(25)01493-x · Cited by 63 · see citing works
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Anliker‐Ort, M., Dingemanse, J., van den Anker, J., & Kaufmann, P. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.599417 · Cited by 52 · see citing works
Complement system activation: bridging physiology, pathophysiology, and therapy
Azoulay, É., Zuber, J., Bousfiha, A. A., Long, Y., Tan, Y. C. R. S., Luo, S., Essafti, M., & Annane, D. (2024) · Intensive Care Medicine · doi:10.1007/s00134-024-07611-4 · Cited by 46 · see citing works
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Elshabrawy, H. A. (2020) · Vaccines · doi:10.3390/vaccines8020335 · Cited by 45 · see citing works
Hammadi, S., Tzoumas, N., Ferrara, M., Meschede, I. P., Lo, K., Harris, C., Lako, M., & Steel, D. H. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12082870 · Cited by 44 · see citing works
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Gando, S., Levi, M. M., & Toh, C. (2025) · Journal of Intensive Care · doi:10.1186/s40560-025-00794-y · Cited by 32 · see citing works
Tsai, I., Lin, W., Yang, Y., Tseng, Y.-L., Lin, Y., Chou, C., & Tsau, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184465 · Cited by 26 · see citing works
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Udovičić, I., Stanojević, I., Djordjevic, D., Zeba, S., Rondović, G., Abazovic, T., Lazic, S., Vojvodić, D., To, K., Abazović, D., et al. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10245815 · Cited by 18 · see citing works
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Mishra, R., Behera, L. M., & Rana, S. (2020) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2020.1820381 · Cited by 17 · see citing works
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Mishra, R., Das, A., & Rana, S. (2020) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2020.1738958 · Cited by 16 · see citing works
Qin, S., Yao, X., Li, W., Wang, C., Xu, W., Gan, Z., Yang, Y., Zhong, A., Wang, B., He, Z., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05814-z · Cited by 15 · see citing works
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Tamiya, S., Yoshikawa, E., Suzuki, K., & Yoshioka, Y. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.602453 · Cited by 10 · see citing works
Gonther, S., Bachmann, M., Goren, I., Huard, A., Weigert, A., Köhl, J., & Mühl, H. (2022) · npj Regenerative Medicine · doi:10.1038/s41536-022-00206-x · Cited by 11 · see citing works
Kirfel, J., Kümpers, C., Fähnrich, A., Heidel, C., Jokić, M., Vlašić, I., Marwitz, S., Goldmann, T., Pasternack, H., Bohnet, S., et al. (2021) · Cancers · doi:10.3390/cancers13184562 · Cited by 8 · see citing works
D’Agnillo, F., Zhang, X., & Williams, M. C. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.06.007 · Cited by 8 · see citing works
Liu, Z., Liang, W., & Pan, Y. (2025) · Autoimmunity Reviews · doi:10.1016/j.autrev.2025.103763 · Cited by 7 · see citing works
Muhammad, A. I., Forcados, G. E., Sani, H., Ndidi, U. S., Adamu, A., Katsayal, B. S., Sadiq, I. Z., Abubakar, Y. S., Sulaiman, I., Abubakar, I. B., et al. (2022) · Journal of Food Biochemistry · doi:10.1111/jfbc.14079 · Cited by 7 · see citing works
Han, Z., Xu, J., Guo, X., Liang, L., Zhang, L., Su, Y., Gao, W., Tang, Q., Chen, L., Chen, Z., et al. (2025) · Small Structures · doi:10.1002/sstr.202400625 · Cited by 6 · see citing works
The GPCR adaptor protein Norbin controls the trafficking of C5aR1 and CXCR4 in mouse neutrophils
Chetwynd, S. A., Ward, R. J., Milligan, G., & Welch, H. C. E. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107940 · Cited by 5 · see citing works
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Cyranka, L., Mariegaard, I., Skjoedt, M., Bayarri‐Olmos, R., Mollnes, T. E., Garred, P., & Rosbjerg, A. (2023) · Journal of Innate Immunity · doi:10.1159/000535084 · Cited by 5 · see citing works
Terrington, I., Cox, O., Copley, P., Eastwood, B., Webb, E., McKenzie, C., Saeed, K. B. A., Morris, A. C., Grocott, M. P. W., & Dushianthan, A. (2025) · Journal of the Intensive Care Society · doi:10.1177/17511437251374816 · Cited by 4 · see citing works
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Yasuda, M., Tanaka, Y., Bando, K., Sugawara, S., & Mizuta, K. (2023) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b22-00766 · Cited by 4 · see citing works
Fujita, Y., Matsumoto, H., Inada, K., Onizawa, M., Saito, K., Sumichika, Y., Yoshida, S., Temmoku, J., Matsuoka, N., Asano, T., et al. (2023) · Immunological Medicine · doi:10.1080/25785826.2023.2292665 · Cited by 4 · see citing works
Fella, E., Papacharalambous, R., Kynigopoulos, D., Ioannou, M., Derua, R., Christodoulou, C. C., Stylianou, M., Karaiskos, C., Kagiava, A., Gerasimou, P., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.947071 · Cited by 4 · see citing works
Zhou, Q., Nishimura, T., Veer, C. V. ′., Leung, L. L. K., & Morser, J. (2025) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2025.05.036 · Cited by 1 · see citing works
Baek, I., Kim, H., Park, K., & Kim, K. (2025) · Arthritis Research & Therapy · doi:10.1186/s13075-025-03598-5 · Cited by 1 · see citing works
The Inflammatory and Barrier Response After Polytrauma
Karasu, E., & Huber-Lang, M. S. (2022) · Springer eBooks · doi:10.1007/978-3-030-95906-7_11 · Cited by 1 · see citing works
Revisitando o Sistema Complemento – Revisão de Literatura
Degasperi, G. R., Paschoal, C. D. S., Aoki, I. S. D. A., & Fernandes, A. M. (2020) · Jornal Interdisciplinar de Biociências · doi:10.26694/jibi.v4i1.7735
Heparin for the Prevention of Preeclampsia: The Role of Non-anticoagulant Mechanisms
Wat, J. M. W. (2020) · TSpace (University of Toronto)
Qin, S., Yao, X., Li, W., Wang, C., Xu, W., Gan, Z., Yang, Y., Zhong, A., Wang, B., He, Z., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1442272/v1
Development of network pharmacology in sepsis treatmentPreprint
chen, F., & chen, M. (2023) · doi:10.22541/au.168491380.08715576/v1
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Pigors, M., Patzelt, S., Brudey, M., Emtenani, S., Khil'chenko, S., Kamaguchi, M., Reichhelm, N., Parker, M., Bieber, K., Ludwig, R. J., et al. (2025) · Biomolecules · doi:10.3390/biom15111549 · Cited by 1 · see citing works
A large-scale profiling study of immune–coagulation associations in rheumatoid arthritis
Zhang, T. Y., Yang, F., Xu, X., Wang, Y., Zhang, Y., & Pan, Z. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1789560
- Authors
- Wood, A. J. T., Vassallo, A., Summers, C., Chilvers, E. R., & Conway‐Morris, A.
- Affiliations
- University of Cambridge (GB)
- Department of Medicine University of Cambridge Cambridge UK
- Corresponding author
- Wood, Alexander J. T.
- ORCID
- Venue
- European Journal of Clinical Investigation
- Publisher
- Wiley
- Published
- 2018-10-15
- Volume
- 48
- Issue
- 12
- Pages
- e13028-e13028
- ISSN
- 0014-2972 (ISSN-L)
- 1365-2362
- OpenAlex
- W2892168129
- Cited by
- 45
- References
- 128
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 2 · 2023: 9 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 2
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- European Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- National Institute on Handicapped Research
- Gates Cambridge Trust
- Wellcome Trust (2055214/Z/16/Z)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- C5a, complement activation, critical illness, organ dysfunction, organ failure, nosocomial infections, innate immunity, inflammation, immune dysfunction, targeted therapy
- MeSH terms
- Anaphylatoxins, Blood Coagulation, Blood Platelets, Cardiovascular System, Cell Communication, Endothelium, Vascular, Humans, Immunity, Innate, Immune System Diseases, Multiple Organ Failure, Complement C5a, Critical Illness, Receptor, Anaphylatoxin C5a
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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