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TheScientificWorldJOURNAL
Volume 10 (2010), Pages 2395-2402
http://dx.doi.org/10.1100/tsw.2010.216
Review Article

Role of C5 Activation Products in Sepsis

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA

Received 10 September 2010; Revised 22 October 2010; Accepted 28 October 2010

Academic Editor: Mauro Perretti

Copyright © 2010 Peter A. Ward.

Abstract

Complement activation products are known to be generated in the setting of both experimental and human sepsis. C5 activation products (C5a anaphylatoxin and the membrane attack complex [MAC] C5b-9) are generated during sepsis following infusion of endotoxin, or after cecal ligation and puncture (CLP), which produces polymicrobial sepsis. C5a reacts with its receptors C5aR and C5L2 in a manner that creates the “cytokine storm”, and is associated with development of multiorgan failure (MOF). A number of other complications arising from the interaction of C5a with its receptors include apoptosis of lymphoid cells, loss of innate immune functions of neutrophils (PMNs, polymorphonuclear leukocytes), cardiomyopathy, disseminated intravascular coagulation, and complications associated with MOF. Neutralization of C5a in vivo or absence/blockade of C5a receptors greatly reduces the adverse events in the setting of sepsis, markedly attenuates MOF, and greatly improves survival. Regarding the possible role of C5b-9 in sepsis, the literature is conflicting. Some studies suggest that C5b-9 is protective, while other studies suggest the contrary. Clearly, in human sepsis, C5a and its receptors may be logical targets for interception.