Expression of human soluble complement receptor 1 by a pig endothelial cell line inhibits lysis by human serum

• Published in: Xenotransplantation (Københaven) 2006-01, Vol.13 (1), p.75-79
• Main Authors: Manzi, Lorna, Montaño, Ramón, Abad, María Jesús, Arsenak, Miriam, Romano, Egidio, Taylor, Peter
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Cell Death; Cell Line; complement; Complement Activation; complement receptor type 1; endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Graft Rejection - prevention & control; Humans; pig; Receptors, Complement - genetics; Receptors, Complement - metabolism; Receptors, Complement 3b - immunology; Serum - metabolism; Swine; Transfection; Transplantation, Heterologous; xenotransplantation
• ISSN: 0908-665X; 1399-3089
• DOI: 10.1111/j.1399-3089.2005.00265.x

: 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 Galα(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.