Display of Fas ligand protein on cardiac vasculature as a novel means of regulating allograft rejection
Display of Fas ligand protein on cardiac vasculature as a novel means of regulating allograft rejection
复制标题
DOI：
10.1161/01.cir.0000064893.96179.7e
复制
发表时间：
2003-03-25
期刊：
影响因子：
37.8
通讯作者：
Shirwan, H
中科院分区：
文献类型：
--
作者：
Akenasy, N;Yolcu, ES;Shirwan, H
Background-Fas ligand (FasL) is a potent death-inducing molecule with important functions in immune homeostasis and tolerance to self-antigens. The complex biological activities of FasL and its inefficient expression using conventional gene transfer approaches limit its use for immunomodulation to prevent allograft rejection. We have recently generated a chimeric FasL with core streptavidin (SA-FasL) with potent apoptotic activity and designed a novel approach to display it on the surface of several cell types via biotinylation. We herein tested whether SA-FasL can also be displayed on vascular endothelial cells in the heart and examined its effect on graft survival after transplantation into syngeneic and allogeneic hosts.Methods and Results-SA-FasL was efficiently displayed on the vasculature of BALB/c hearts with a half-life of 9 days in vivo. Transplantation of hearts displaying SA-FasL into syngeneic hosts resulted in indefinite graft survival without detectable toxicity to the grafts and hosts. In contrast, transplantation of allogeneic C57BL/10 hearts displaying SA-FasL into BALB/c recipients resulted in graft rejection, but in a delayed fashion as compared with control hearts (mean survival time=17.4+/-5 versus 9.6+/-1 days). Allograft survival was further extended to 21+/-2.6 and 24+/-3 days (P
