Anti-CD11d antibody treatment reduces free radical formation and cell death in the injured spinal cord of rats

被引:75
作者
Bao, F [1 ]
Dekaban, GA [1 ]
Weaver, LC [1 ]
机构
[1] John P Robarts Res Inst, Biotherapeut Res Grp, Lab Spinal Cord Injury, Spinal Cord Injury Team, London, ON N6A 5K8, Canada
关键词
caspase-3; hydroethidine; hydroxynonenal; NADPH; phagocyte; 2 '-7 '-dichlorofluorescein;
D O I
10.1111/j.1471-4159.2005.03280.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Treatment with a monoclonal antibody (mAb) against the CD11d subunit of the leukocyte integrin CD11d/CD18 after spinal cord injury (SCI) decreases intraspinal inflammation and oxidative damage, improving neurological function in rats. In this study we tested whether the anti-CD11d mAb treatment reduces intraspinal free radical formation and cell death after SCI. Using clip-compression SCI in rats, reactive oxygen species (ROS) generated in injured spinal cord were detected using 2',7'-dichlorofluorescin-diacetate and hydroethidine as fluorescent probes. ROS in the injured cord increased significantly after SCI; anti-CD11d mAb treatment significantly reduced this ROS formation. Immunohistochemistry and western blotting were employed to assess the effects of anti-CD11d mAb treatment on spinal cord expression of gp91(Phox) (a subunit of NADPH oxidase producing superoxide) on formation of 4-hydroxynonenal (HNE, indicating lipid peroxidation) and on expression of caspase-3. We also assessed effects on cell death, determined by cell morphology. The expression of gp91(Phox), formation of HNE, and cell death increased after SCI. Anti-CD11d mAb treatment clearly attenuated these responses. In conclusion, anti-CD11d mAb treatment significantly reduces intraspinal free radical formation caused by infiltrating leukocytes after SCI, thereby reducing secondary cell death. These effects likely underlie tissue preservation and improved neurological function that result from the mAb treatment.
引用
收藏
页码:1361 / 1373
页数:13
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