Decay-Accelerating Factor Attenuates C-Reactive Protein-Potentiated Tissue Injury After Mesenteric Ischemia/Reperfusion

Background. C-reactive protein (CRP) is an acute pro-inflammatory mediator that has been demon-strated 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 expres-sion of tissue injury following IR, we have investigated the effects of human decay-accelerating factor (DAF), a complement inhibitor, on CRP-potentiated comple-ment activation and tissue injury in mice subjected to mesenteric IR. Materials and Methods. Male C57B1/6 mice were al-located 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 infiltra-tion, myeloperoxidase (MPO) expression, complement component deposition, and interleukin-6 (IL-6) pro-duction were assessed for each treatment group of mice. Results. We report that administration of DAF sig-nificantly attenuates the CRP-enhanced intestinal in-jury as well as remote lung damages following acute mesenteric IR inmice, while DAF inhibits complement activation, suppresses neutrophil infiltration, and re-duces IL-6 production. Conclusions. Our study suggests that inhibition complement activation with DAF may prove useful for the treatment of post-ischemic inflammatory in-juries associated with an increased production of CRP. Published by Elsevier Inc. Key Words: complement; C-reactive protein; inflam