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 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.


METHODS
Male C57B1/6 mice were allocated into eight groups: (1) Sham-operated group without IR injury; (2) CRP+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 injuries associated with an increased production of CRP.
Lu
Xinyue
X
Division of Military Casualty Research, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Li
Yansong
Y
Simovic
Milomir O
MO
Peckham
Russell
R
Wang
Ying
Y
Tsokos
George C
GC
Dalle Lucca
Jurandir J
JJ
D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D018958:CD55 Antigens / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015936:Complement C5a / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008643:Mesentery / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*
D018958:CD55 Antigens; D015938:Complement Membrane Attack Complex; D015850:Interleukin-6; C047610:SC5b-9 protein complex; D015936:Complement C5a; D002097:C-Reactive Protein; D009195:Peroxidase