Complement factor 3 deficiency attenuates hemorrhagic shock-related hepatic injury and systemic inflammatory response syndrome

Changchun Cai, Roop Gill, Hyun Ae Eum, Zongxian Cao, Patricia A. Loughran, Sophie Darwiche, Rebecca D. Edmonds, Christoph L. Menzel, Timothy R. Billiar

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28 Scopus citations


Although complement activation is known to occur in the setting of severe hemorrhagic shock and tissue trauma (HS/T), the extent to which complement drives the initial inflammatory response and end-organ damage is uncertain. In this study, complement factor 3-deficient (C3-/-) mice and wild-type control mice were subjected to 1.5-h hemorrhagic shock, bilateral femur fracture, and soft tissue injury, followed by 4.5-h resuscitation (HS/T). C57BL/6 mice were also given 15 U of cobra venom factor (CVF) or phosphate-buffered saline injected intraperitoneally, followed by HS/T 24 h later. The results showed that HS/T resulted in C3 consumption in wild-type mice and C3 deposition in injured livers. C3-/- mice had significantly lower serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and circulating DNA levels, together with much lower circulating interleukin (IL)-6, IL-10, and high-mobility group box 1 (HMGB1) levels. Temporary C3 depletion by CVF preconditioning also led to reduced transaminases and a blunted cytokine release. C3-/- mice displayed well-preserved hepatic structure. C3-/- mice subjected to HS/T had higher levels of heme oxygenase-1, which has been associated with tissue protection in HS models. Our data indicate that complement activation contributes to inflammatory pathways and liver damage in HS/T. This suggests that targeting complement activation in the setting of severe injury could be useful.

Original languageEnglish
Pages (from-to)R1175-R1182
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number5
StatePublished - Nov 2010
Externally publishedYes


  • Double-strand DNA
  • Heme oxygenase-1
  • High-mobility group box 1
  • Single-strand DNA
  • Systemic inflammatory response syndrome


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