Expression of human soluble complement receptor 1 by a pig endothelial cell line inhibits lysis by human serum.
The importance of complement activation and naturally occurring anti-pig antibodies in the hyperacute rejection (HAR) observed in models of pig-to-human xenotransplantation is well established. To overcome this, much effort has been dedicated to preparing transgenic pigs by knocking out Galalpha(1-3)Gal expression in these animals, or knocking in the expression of human complement regulatory proteins (CRPs), such as CD59 or decay accelerating factor. A soluble form of another membrane CRP, complement receptor type 1 (CR1), has also been shown to inhibit complement activation. Here, we show that transfection of a pig endothelial cell line with a truncated form of human soluble complement receptor 1 (sCR1) almost completely protected these cells from complement-mediated lysis by human AB serum. Pigs genetically manipulated to express human sCR1 may represent an additional strategy to inhibit HAR of pig-to-human transplanted organs.
Laboratory of Cellular and Molecular Pathology, Centre for Experimental Medicine, Venezuelan Institute for Scientific Research (IVIC), Caracus, Venezuela.
Lorna
L
Manzi
Ramón
R
Montaño
María Jesús
MJ
Abad
Miriam
M
Arsenak
Egidio
E
Romano
Peter
P
Taylor
D000818:Animals; D030801:Animals, Genetically Modified; D016923:Cell Death; D002460:Cell Line; D003167:Complement Activation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism*; D017463:Receptors, Complement 3b / Q000276:immunology; D044967:Serum / Q000378:metabolism*; D013552:Swine; D014162:Transfection; D014183:Transplantation, Heterologous
D011951:Receptors, Complement; D017463:Receptors, Complement 3b