Document Detail

Complement depletion protects lupus-prone mice from ischemia reperfusion-initiated organ injury.
MedLine Citation:
PMID:  23104558     Owner:  NLM     Status:  Publisher    
Ischemia reperfusion injury causes a vigorous immune response that is amplified by complement activation leading to local and remote tissue damage. Using MRL/lpr mice that are known to experience accelerated tissue damage after mesenteric ischemia reperfusion injury we sought to evaluate whether complement inhibition mitigates organ damage. We found that complement depletion with cobra venom factor protected mice from local and remote lung tissue damage. Protection from injury was associated with less C3 and membrane attack complex deposition, less neutrophil infiltration and lower levels of local pro-inflammatory cytokine production. In addition, complement depletion was able to decrease the level of oxidative stress as measured by GPX-1 mRNA levels and superoxide dismutase activity. Furthermore, blockage of C5a receptor protected MRL/lpr mice from local tissue damage but not from remote lung tissue damage. In conclusion, although both treatments with cobra venom factor and C5a receptor antagonist were able to protect mice from local tissue damage, treatment with C5a receptor antagonist was not able to protect mice from remote lung tissue damage implying that more factors contribute to the development of remote tissue damage after ischemia reperfusion injury. These data also suggest that complement inhibition at earlier rather than late stages can have clinical benefit in clinical conditions that are complicated with ischemia reperfusion injury.
Antonis Ioannou; Linda A Lieberman; Jurandir J Dalle Lucca; George C Tsokos
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-25
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  -     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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