Article

Complement component C5a mediates hemorrhage-induced intestinal damage.

Division of Biology, Kansas State University, Manhattan, Kansas 66506, USA.
Journal of Surgical Research (impact factor: 2.25). 12/2008; 150(2):196-203. DOI:10.1016/j.jss.2008.02.010 pp.196-203
Source: PubMed

ABSTRACT Complement has been implicated in the pathogenesis of intestinal damage and inflammation in multiple animal models. Although the exact mechanism is unknown, inhibition of complement prevents hemodynamic alterations in hemorrhage.
C57Bl/6, complement 5 deficient (C5-/-) and sufficient (C5+/+) mice were subjected to 25% blood loss. In some cases, C57Bl/6 mice were treated with C5a receptor antagonist (C5aRa) post-hemorrhage. Intestinal injury, leukotriene B4, and myeloperoxidase production were assessed for each treatment group of mice.
Mice subjected to significant blood loss without major trauma develop intestinal inflammation and tissue damage within 2 hours. We report here that complement 5 (C5) deficient mice are protected from intestinal tissue damage when subjected to hemorrhage (injury score = 0.36 compared with wildtype hemorrhaged animal injury score = 2.89; P < 0.05). We present evidence that C5a represents the effector molecule because C57Bl/6 mice treated with a C5a receptor antagonist displayed limited intestinal injury (injury score = 0.88), leukotriene B4 (13.16 pg/mg tissue), and myeloperoxidase (115.6 pg/mg tissue) production compared with hemorrhaged C57Bl/6 mice (P < 0.05).
Complement activation is important in the development of hemorrhage-induced tissue injury and C5a generation is critical for tissue inflammation and damage. Thus, therapeutics targeting C5a may be useful therapeutics for hemorrhage-associated injury.

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Keywords

25% blood loss
 
C5a generation
 
C5a receptor antagonist
 
C5aRa
 
Complement
 
complement 5
 
Complement activation
 
hemodynamic alterations
 
hemorrhage-induced tissue injury
 
hemorrhaged C57Bl/6 mice
 
injury score
 
intestinal inflammation
 
intestinal tissue damage
 
multiple animal models
 
myeloperoxidase production
 
significant blood loss
 
tissue damage
 
tissue inflammation
 
treatment group
 
wildtype hemorrhaged animal injury score