Complement component C5a mediates hemorrhage-induced intestinal damage

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dc.contributor.author Fleming, Sherry D.
dc.contributor.author Phillips, Lauren M.
dc.contributor.author Lambris, John D.
dc.contributor.author Tsokos, George C.
dc.date.accessioned 2013-12-04T22:45:22Z
dc.date.available 2013-12-04T22:45:22Z
dc.date.issued 2013-12-04
dc.identifier.uri http://hdl.handle.net/2097/16952
dc.description.abstract Background: 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. Materials/Methods: 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. Results: Mice subjected to significant blood loss without major trauma develop intestinal inflammation and tissue damage within two 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 to 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 to hemorrhaged C57Bl/6 mice (p<0.05). Conclusion: 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. en_US
dc.language.iso en_US en_US
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S0022480408000887 en_US
dc.subject Complement en_US
dc.subject Mucosa en_US
dc.subject Rodent en_US
dc.title Complement component C5a mediates hemorrhage-induced intestinal damage en_US
dc.type Article (author version) en_US
dc.date.published 2008 en_US
dc.citation.doi doi:10.1016/j.jss.2008.02.010 en_US
dc.citation.epage 203 en_US
dc.citation.issue 2 en_US
dc.citation.jtitle Journal of Surgical Research en_US
dc.citation.spage 196 en_US
dc.citation.volume 150 en_US
dc.contributor.authoreid sdflemin en_US


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