Decay-Accelerating Factor Attenuates C-Reactive Protein-Potentiated Tissue Injury After Mesenteric Ischemia/Reperfusion
Abstract
Background. C-reactive protein (CRP) is an acute pro-inflammatory mediator that has been demonstrated to enhance ischemia/reperfusion (IR) injury by virtue of activating the complement system. CRP is able to interact with complement proteins such as C1q, complement factor H, and C4b-binding protein. Since complement activation is central in the expression of tissue injury following IR, we have investigated the effects of human decay-accelerating factor (DAF), a complement inhibitor, on CRP-potentiated complement activation and tissue injury in mice subjected to mesenteric IR. Materials and Methods. Male C57B1/6 mice were allocated into eight groups: (1) Sham-operated group without IR injury; (2) CRPDSham group; (3) IR group; (4) CRPDIR group; (5) DAF group; (6) CRPDDAF group; (7) IRDDAF group, and (8) CRPDIRDDAF group. Intestinal and lung injury, neutrophil infiltration, myeloperoxidase (MPO) expression, complement component deposition, and interleukin-6 (IL-6) production were assessed for each treatment group of mice. Results. We report that administration of DAF significantly attenuates the CRP-enhanced intestinal injury as well as remote lung damages following acute mesenteric IR in mice, while DAF inhibits complement activation, suppresses neutrophil infiltration, and reduces IL-6 production. Conclusions. Our study suggests that inhibition complement activation with DAF may prove useful for the treatment of post-ischemic inflammatory injuries associated with an increased production of CRP.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2011
- Accession Number
- ADA619250
Entities
People
- George C. Tsokos
- Jurandir J. Dalle Lucca
- Milomir O. Simovic
- Russell Peckham
- Xinyue Lu
- Yansong Li
- Ying Wang
Organizations
- Walter Reed Army Institute of Research