Prevention of hyperacute rejection by phosphatidylinositol-anchored mini-complement receptor type 1.
Complement receptor type 1 (CR1, CD35) contains both factor I cofactor activity and convertase decay accelerating activity, but is, in general, thought to be an extrinsic regulator of complement activation. In this study, we prepared a phosphatidylinositol (PI)-anchored mini-CR1, which is composed of the short consensus repeat (SCR) 8-11 of CR1 and the PI anchor of DAF, and expressed it stably on a swine endothelial cell (SEC) line. We then examined the intrinsic regulatory activity of the mini-CR1, with respect to complement-mediated cell lysis as an in vitro hyperacute rejection model of a swine to human discordant xenograft. Flowcytometric profiles of the stable SEC lines with mini-CR1 showed a moderate level of expression for this molecule. Mini-CR1 blocked human complement-mediated cell lysis by approximately 50-70% on SEC. From the data of this study and our previous studies, mini-CR1 was more effective than membrane cofactor protein (MCP, CD46), and as effective as decay accelerating factor (DAF, CD55) in this system. The results suggest that PI-anchored mini-CR1 represents a useful molecule for clinical xenotransplantation.
Mikata
S
S
Division of Organ Transplantation, Osaka University, Suita, Japan.
Miyagawa
S
S
Yoshitatsu
M
M
Ikawa
M
M
Okabe
M
M
Matsuda
H
H
Shirakura
R
R
D000818:Animals; D018958:CD55 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D017463:Receptors, Complement 3b / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013552:Swine; D014162:Transfection; D014183:Transplantation, Heterologous / Q000276:immunology*
D018958:CD55 Antigens; D018076:DNA, Complementary; D017261:Glycosylphosphatidylinositols; D017463:Receptors, Complement 3b