Accession Number:

ADA614702

Title:

Complement Depletion Protects Lupus-prone Mice from Ischemia-reperfusion-initiated Organ Injury

Descriptive Note:

Journal article

Corporate Author:

ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX

Report Date:

2012-10-25

Pagination or Media Count:

11.0

Abstract:

Ischemia-reperfusion IR injury causes a vigorous immune response that is amplified by complement activation, leading to local and remote tissue damage. Using MRLlpr mice, which are known to experience accelerated tissue damage after mesenteric IR 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 complement C3 and membrane attack complex deposition, less neutrophil infiltration, and lower levels of local proinflammatory cytokine production. In addition, complement depletion was able to decrease the level of oxidative stress as measured by glutathione peroxidase 1 mRNA levels and superoxide dismutase activity. Furthermore, blockage of C5a receptor protected MRLlpr mice from local tissue damage, but not from remote lung tissue damage. In conclusion, although 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 IR injury. These data also suggest that complement inhibition at earlier, rather than late, stages can have clinical benefit in conditions that are complicated with IR injury.

Subject Categories:

  • Biology
  • Anatomy and Physiology
  • Medicine and Medical Research
  • Medical Facilities, Equipment and Supplies

Distribution Statement:

APPROVED FOR PUBLIC RELEASE