[Coexpression of human complement regulatory protein genes, CD59 and MCP in transgenic mice protects isolated mouse heart function in ex vivo human plasma perfusion model].
OBJECTIVE
To investigate if the expression of human complement regulatory protein genes in transgenic donor protects against hyperacute rejection (HAR) in the recipient.


METHODS
Kunming mice were transfected with 2 human complement regulatory protein genes, CD59 and MCP, so as to establish a transgenic hCD59/hMCP mouse model. Eight hCD59 expression mice, 11 hMCP expression mice, and 8 hCD59/hMCP expression mice were used as experimental groups, and 10 transgenic negative littermates were used as control group. The hearts of the mice were taken out to be perfused with 10% pooled human blood of B type. During the perfusion electrocardiography was carried out to observe the beating time. After the hearts stopped beating, immunofluorescence staining and immunohistochemistry were used to detect the deposition of complements C(9) and C(3c) in the heart tissue.


RESULTS
The mean heart beating time was 138 +/- 25 minutes in the hCD59/hMCP expression group, 78 +/- 27 minutes in the hCD59 expression group, 43 +/- 21 minutes in the hMCP group, and 20 +/- 12 minutes in the wild type nontransgenic control group (all P < 0.01, Dennett's T test for all 3 other groups relative to the hCD59/hMCP group). Deposition of the complement C(9) and that of C(3c) were not found in the hearts of the hCD59/hMCP group, however, could be found in the hearts of the 2 monotransgenic groups and nontransgenic group.


CONCLUSIONS
The coexpression of human complement regulatory protein genes, CD59 and MCP in the xenografts effectively inhibits the complement of xenograft-mediated HAR.
Xie
Lin
L
Institute of Organ Transplantation, Key Laborary of Organ Transplantation (HUST), Ministry of Education, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhu
Min
M
Wang
Shu-sen
SS
Li
Rong
R
Zeng
Meng-hua
MH
Huang
Ya-bing
YB
Wang
Lu
L
Guo
Hui
H
Wei
Qing-xin
QX
Li
Wen-xin
WX
Chen
Shi
S
D000818:Animals; D018957:CD59 Antigens / Q000096:biosynthesis / Q000235:genetics*; D004562:Electrocardiography; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051916:Membrane Cofactor Protein / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion / Q000379:methods; D010949:Plasma
D018957:CD59 Antigens; D051916:Membrane Cofactor Protein