Thurman Joshua M, Royer Pamela A, Ljubanovic Danica, Dursun Belda, Lenderink Amanda M, Edelstein Charles L, Holers V Michael
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA, and Department of Pathology, University Hospital Dubrava, Zabreb, Croatia.
J Am Soc Nephrol. 2006 Mar;17(3):707-15. doi: 10.1681/ASN.2005070698. Epub 2006 Feb 8.
Complement activation in the kidney after ischemia/reperfusion (I/R) seems to occur primarily via the alternative complement pathway. The ability of an inhibitory mAb to mouse factor B, a necessary component of the alternative pathway, to protect mice from ischemic acute renal failure was tested. Treatment with the mAb prevented the deposition of C3b on the tubular epithelium and the generation of systemic C3a after renal I/R. Treated mice had significantly lower increases in serum urea nitrogen and developed significantly less morphologic injury of the kidney after I/R. For gaining insight into potential mechanisms of protection, the activity of caspases within the kidney also was measured, and it was found that caspases-2, -3, and -9 increased in a complement-dependent manner after renal I/R. Apoptotic cells were detected by terminal deoxynucleotidyl transferase catalyzed labeling of DNA fragments, and mice in which the alternative pathway was inhibited demonstrated significantly less apoptosis than control mice. Thus, use of an inhibitory mAb to mouse factor B effectively prevented activation of complement in the kidney after I/R and protected the mice from necrotic and apoptotic injury of the tubules.
缺血/再灌注（I/R）后肾脏中的补体激活似乎主要通过替代补体途径发生。测试了一种针对小鼠补体因子B（替代途径的必要成分）的抑制性单克隆抗体保护小鼠免受缺血性急性肾衰竭的能力。用该单克隆抗体治疗可防止肾I/R后C3b在肾小管上皮细胞上的沉积以及全身C3a的产生。经治疗的小鼠血清尿素氮升高明显较低，并且在I/R后肾脏发生的形态学损伤明显较少。为了深入了解潜在的保护机制，还测量了肾脏中半胱天冬酶的活性，发现肾I/R后半胱天冬酶-2、-3和-9以补体依赖的方式增加。通过末端脱氧核苷酸转移酶催化的DNA片段标记检测凋亡细胞，与对照小鼠相比，替代途径受到抑制的小鼠显示出明显较少的细胞凋亡。因此，使用针对小鼠因子B的抑制性单克隆抗体可有效防止I/R后肾脏中补体的激活，并保护小鼠免受肾小管坏死和凋亡损伤。
