Expression of complement regulatory proteins in accommodated xenografts induced by anti-alpha-Gal IgG1 in a rat-to-mouse model.
Anti-graft antibodies are often associated with graft rejection. Under special conditions, grafts continue to function normally even in the presence of anti-graft antibodies and complement. This condition is termed accommodation. We developed a xenograft accommodation model in which baby Lewis rat hearts are transplanted into Rag/GT-deficient mice, and accommodation is induced by repeated i.v. injections of low-dose anti-alpha-Gal IgG(1). The accommodated grafts survived a bolus dose of anti-alpha-Gal IgG(1), while freshly transplanted second grafts were rejected. To study the mechanism of anti-alpha-Gal IgG(1)-mediated accommodation, both real-time PCR and immunohistochemical staining revealed elevated expression of DAF, Crry and CD59 in the accommodated grafts. In vitro exposure of rat endothelial cells to anti-alpha-Gal IgG(1) also induced the up-regulation of DAF, Crry and CD59, as revealed by Western blot analyses, and was associated with an acquired resistance to antibody and complement-mediated lysis in vitro. Collectively, these studies suggest that the up-regulation of complement regulatory proteins may abrogate complement-mediated rejection and permit the development of xenograft accommodation.
Ding
J Wen
JW
Section of Transplantation, Department of Surgery, University of Chicago, Chicago, IL, USA.
Zhou
T
T
Ma
L
L
Yin
D
D
Shen
J
J
Ding
C P Y
CP
Tang
I Y
IY
Byrne
G W
GW
Chong
A S
AS
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000502:physiology; D018957:CD59 Antigens / Q000096:biosynthesis* / Q000502:physiology; D002478:Cells, Cultured; D003167:Complement Activation / Q000276:immunology*; D007074:Immunoglobulin G / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000502:physiology; D023001:Transplantation Tolerance / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D000519:alpha-Galactosidase / Q000276:immunology*
D000954:Antigens, Surface; D018957:CD59 Antigens; C513105:Cr1l protein, rat; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; D000519:alpha-Galactosidase