Improved suppression of circulating complement does not block acute vascular rejection of pig-to-rhesus monkey cardiac transplants

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	Improved suppression of circulating complement does not block acute vascular rejection of pig-to-rhesus monkey cardiac transplants
	Chen G 1; Sun QY 2; Wang XM 1; Shen SQ 1; Guo H 1; Wang H 1; Wu Y 1; Wang WY 2; Xiong YL 2; Chen S*1; schen@tjh.tjmu.edu.cn
	2004
发表期刊	XENOTRANSPLANTATION
ISSN	0908-665X
卷号	11 期号:2 页码:123-132
合作性质	其它
摘要	At present, acute vascular rejection (AVR) remains a primary obstacle inhibiting long-term graft survival in the pig-to-non-human primate transplant model. The present study was undertaken to determine whether repetitive injection of low dose Yunnan-cobra venom factor (Y-CVF), a potent complement inhibitor derived from the venom of Naja kaouthia can completely abrogate hemolytic complement activity and subsequently improve the results in a pig-to-rhesus monkey heterotopic heart transplant model. Nine adult rhesus monkeys received a heterotopic heart transplant from wild-type pigs and the recipients were allocated into two groups: group 1 (n = 4) received repetitive injection of low dose Y-CVF until the end of the study and group 2 (n = 5) did not receive Y-CVF. All recipients were treated with cyclosporine A (CsA), cyclophosphamide (CyP) and steroids. Repetitive Y-CVF treatment led to very dramatic fall in CH50 and serum C3 levels (CH50 < 3 units/C3 remained undetectable throughout the experiment) and successfully prevented hyperacute rejection (HAR), while three of five animals in group 2 underwent HAR. However, the continuous suppression of circulating complement did not prevent AVR and the grafts in group 1 survived from 8 to 13 days. Despite undetectable C3 in circulating blood, C3 deposition was present in these grafts. The venular thrombosis was the predominant histopathologic feature of AVR. We conclude that repetitive injection of low dose Y-CVF can be used to continuously suppress circulating complement in a very potent manner and successfully prevent HAR. However, this therapy did not inhibit complement deposition in the graft and failed to prevent AVR. These data suggest that using alternative pig donors [i.e. human decay accelerating factor (hDAF)-transgenic] in combination with the systemic use of complement inhibitors may be necessary to further control complement activation and improve survival in pig-to-non-human primate xenotransplant model.
关键词	Acute Vascular Rejection Heart Transplantation Pig-to-rhesus Monkey Model Xenotransplantaion Yunnan-cobra Venom Factor
资助者	This study was supported by a grant ‘‘National Natural Science Foundation of China (39993434)’’ and by ‘‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’’. ; This study was supported by a grant ‘‘National Natural Science Foundation of China (39993434)’’ and by ‘‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’’. ; This study was supported by a grant ‘‘National Natural Science Foundation of China (39993434)’’ and by ‘‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’’. ; This study was supported by a grant ‘‘National Natural Science Foundation of China (39993434)’’ and by ‘‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’’.
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收录类别	SCI
资助者	This study was supported by a grant ‘‘National Natural Science Foundation of China (39993434)’’ and by ‘‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’’. ; This study was supported by a grant ‘‘National Natural Science Foundation of China (39993434)’’ and by ‘‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’’. ; This study was supported by a grant ‘‘National Natural Science Foundation of China (39993434)’’ and by ‘‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’’. ; This study was supported by a grant ‘‘National Natural Science Foundation of China (39993434)’’ and by ‘‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’’.
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/5325
专题	其他
通讯作者	schen@tjh.tjmu.edu.cn
作者单位	1.Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2.Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
推荐引用方式 GB/T 7714	Chen G,Sun QY,Wang XM,et al. Improved suppression of circulating complement does not block acute vascular rejection of pig-to-rhesus monkey cardiac transplants[J]. XENOTRANSPLANTATION,2004,11(2):123-132.
APA	Chen G.,Sun QY.,Wang XM.,Shen SQ.,Guo H.,...&schen@tjh.tjmu.edu.cn.(2004).Improved suppression of circulating complement does not block acute vascular rejection of pig-to-rhesus monkey cardiac transplants.XENOTRANSPLANTATION,11(2),123-132.
MLA	Chen G,et al."Improved suppression of circulating complement does not block acute vascular rejection of pig-to-rhesus monkey cardiac transplants".XENOTRANSPLANTATION 11.2(2004):123-132.

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