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Role of C5a and C5a Receptor in Sepsis

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Book cover The Complement System

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Abstract

In experimental sepsis (after cecal ligation and puncture, CLP) there is convincing evidence of complement activation, as there is in human sepsis. In addition, in sepsis involving rodents and humans, blood neutrophils have lost innate immune functions (chemotaxis, phagocytosis, the ability to produce H2O2). In CLP, and in neutrophils exposed to the complement anaphylatoxin, C5a, there is defective activation of MAPK (mitogen activated protein kinase), phosphorylation of p47, and inability to assemble NADPH oxidase. In experimental sepsis, the consumptive coagulopathy can be prevented by anti-C5a. Sepsis is also associated with loss of C5a receptor (C5aR) on neutrophils. In sepsis, thymocytes undergo apoptosis that is C5a mediated. All of these abnormalities occurring in experimental sepsis can be reversed by treatment with anti-C5a, with C5aR antagonist, with anti-C5aR, or with anti-IL-6, which causes upregulation of C5aR. These data suggest that generation of C5a during sepsis is harmful and that its interception or blockade of C5aR is beneficial.

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Authors and Affiliations

  1. Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109

    F. S. Zetoune & P. A. Ward

  2. Department of Trauma, Hand and Reconstructive Surgery, University of Ulm, Ulm, Germany

    M. S. Huber-Lang

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  1. F. S. Zetoune
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  2. P. A. Ward
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  3. M. S. Huber-Lang
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  1. Walter Reed Army Institute of Research, Silver Spring, MD

    Janos Szebeni

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Zetoune, F.S., Ward, P.A., Huber-Lang, M.S. (2004). Role of C5a and C5a Receptor in Sepsis. In: Szebeni, J. (eds) The Complement System. Springer, Boston, MA. https://doi.org/10.1007/1-4020-8056-5_21

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  • DOI: https://doi.org/10.1007/1-4020-8056-5_21

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4020-8055-5

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