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

作者：Lu Xinyue; Li Yansong; Simovic Milomir O; Peckham Russell; Wang Ying; Tsokos George C; Lucca Jurandir J Dalle^*

来源：Journal of Surgical Research, 2011, 167(2): E103-E115.

DOI：10.1016/j.jss.2009.10.021

• complement
• C-reactive protein
• inflammation
• rodent
• mesenteric ischemia

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) CRPD+Sham group; (3) IR group; (4) CRP+IR group; (5) DAF group; (6) CRP+DAF group; (7) IR+DAF group, and (8) CRP+IR+DAF 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 in-juries associated with an increased production of CRP. Published by Elsevier Inc.

• 出版日期2011-5