The effect of soluble complement receptor type 1 on hyperacute allograft rejection.
The effect of soluble complement receptor type 1 on hyperacute allograft rejection.
复制标题
可溶性补体受体1型对超急性同种异体移植排斥的影响。
DOI：
10.1016/0022-4804(91)90202-w
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Bollinger,RR
中科院分区：
文献类型：
--
作者：
Pruitt,SK;Bollinger,RR
致敏受体器官移植成功的主要障碍是抗体介导的超急性排斥反应。我们假设，在多个阶段抑制补体级联激活的人重组可溶性补体受体1 （sCR1）会延迟这一过程。采用成熟的超急性排斥反应模型，21只Lewis大鼠每只接受三次连续的ACI大鼠皮肤移植，结果血清中ACI特异性抗体滴度高。这些过敏的Lewis大鼠接受异位ACI心脏异体移植。在同种异体移植物再灌注之前，立即静脉注射3mg /kg （n= 11）的sCR1或等量的磷酸盐缓冲盐水（PBS） （n= 10）。同种异体移植物再灌注后5分钟，sCR1组溶血补体活性降低63±2% (SEM)， PBS组降低25±3% （P< 0.0001， Wilcoxon秩和检验（WRST））。sCR1组移植物存活时间延长至32.0±4.47小时，PBS组为3.25±0.81小时（P< 0.0001， WRST）。同种异体移植物的连续组织学检查显示，sCR1治疗可阻止同种异体移植物冠状血管腔内血小板血栓的早期发展。本研究表明，单次3mg /kg剂量的sCR1可显著延长超敏Lewis大鼠移植心脏ACI的存活时间。由sCR1介导的补体失活可能对致敏受体的移植有用。
A major obstacle to successful organ transplantation in sensitized recipients is antibody-mediated hyperacute rejection. We hypothesized that human recombinant soluble complement receptor type 1 (sCR1), which inhibits activation of the complement cascade at multiple stages, would delay this process. Using a well-established model of hyperacute rejection, 21 Lewis rats each received three successive ACI rat skin grafts which resulted in high serum titers of ACI-specific antibodies. These hypersensitized Lewis rats then received heterotopic ACI cardiac allografts. Immediately prior to allograft reperfusion, sCR1 at 3 mg/kg (n= 11) or an equivalent volume of phosphate-buffered saline (PBS) (n= 10) was administered intravenously. Five minutes following allograft reperfusion, hemolytic complement activity was reduced by 63 ± 2% (SEM) in the sCR1 group vs 25 ± 3% in the PBS group (P< 0.0001, Wilcoxon rank sum test (WRST)). Graft survival in the sCR1 group was prolonged to 32.0 ± 4.47 hr vs 3.25 ± 0.81 hr in the PBS group (P< 0.0001, WRST). Serial histologic examination of allografts showed that sCR1 therapy prevented the early development of luminal platelet thrombi in the allograft coronary vessels. This study demonstrates that a single 3 mg/kg dose of sCR1 significantly prolongs ACI cardiac allograft survival in the hypersensitized Lewis rat recipient. Complement inactivation, mediated by sCR1, may prove useful for transplantation in sensitized recipients.