Antibody-mediated rejection(ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation(ITx). Compelling evidence indicates that donor-specific antibodies can mediate and pr...Antibody-mediated rejection(ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation(ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibodymediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation.展开更多
Objective:To establish the polytransgenic mice expressing the human HT and complement regulatory proteins (CRPs) and discuss their ability to resist the hyperacute rejection (HAR) and delayed xenograft rejection (DXR)...Objective:To establish the polytransgenic mice expressing the human HT and complement regulatory proteins (CRPs) and discuss their ability to resist the hyperacute rejection (HAR) and delayed xenograft rejection (DXR) of heterogenic transplantation. Methods:Transgenic mice were produced by microinjection to construct gene for human HT, delay acceleration factor (DAF) and/or CD59 into the male pronucleus of zygote. PCR and Southern blot were used to screen the positive transgenic mice. Flow cytometry (FCM) was used to detect the expression of HT, α-Gal and DAF or CD59 on the PBMCs of transgenic mice. The survival time and function of the heart of transgenic mice were determined by a modified Langendorff cardiac perfusion apparatus. The change of proteinosis on IgM、IgG、C3c and C9 from different cardiac vascular endothelial cells of transgenic mice were detected by immunohistochemistry. Results:HT,DAF or CD59 were highly expressed on the positive transgenic mice by FCM. The deposition of IgM、IgG、C3c or C9 in the cardiac vascular endothelial cells of the positive transgenic mice were decreased. The survival time and function of the heart of the co-transgenic mice with AB serum perfusion were significantly longer and higher than that of the single HT positive transgenic mice(P<0.05). Conclusion:The mice co-expressing HT/DAF or HT/CD59 couldresist the HAR,which was better than those expressing HT alone. It is feasible to use HT and CRPs co-transgenic methods to resist the HAR and DXR.展开更多
基金Supported by The grant from the National Natural Science Foundation of China,No.81570588
文摘Antibody-mediated rejection(ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation(ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibodymediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation.
基金Tianjin Municipal Science and Technology CommissionGrant number:043803411
文摘Objective:To establish the polytransgenic mice expressing the human HT and complement regulatory proteins (CRPs) and discuss their ability to resist the hyperacute rejection (HAR) and delayed xenograft rejection (DXR) of heterogenic transplantation. Methods:Transgenic mice were produced by microinjection to construct gene for human HT, delay acceleration factor (DAF) and/or CD59 into the male pronucleus of zygote. PCR and Southern blot were used to screen the positive transgenic mice. Flow cytometry (FCM) was used to detect the expression of HT, α-Gal and DAF or CD59 on the PBMCs of transgenic mice. The survival time and function of the heart of transgenic mice were determined by a modified Langendorff cardiac perfusion apparatus. The change of proteinosis on IgM、IgG、C3c and C9 from different cardiac vascular endothelial cells of transgenic mice were detected by immunohistochemistry. Results:HT,DAF or CD59 were highly expressed on the positive transgenic mice by FCM. The deposition of IgM、IgG、C3c or C9 in the cardiac vascular endothelial cells of the positive transgenic mice were decreased. The survival time and function of the heart of the co-transgenic mice with AB serum perfusion were significantly longer and higher than that of the single HT positive transgenic mice(P<0.05). Conclusion:The mice co-expressing HT/DAF or HT/CD59 couldresist the HAR,which was better than those expressing HT alone. It is feasible to use HT and CRPs co-transgenic methods to resist the HAR and DXR.
