Expression of complement regulatory proteins in accommodated xenografts induced by anti-alpha-Gal IgG1 in a rat-to-mouse model.

Ding JW, Zhou T, Ma L, Yin D, Shen J, Ding CP, Tang IY, Byrne GW, Chong AS
Am J Transplant. 2008 8 (1): 32-40

PMID: 17973967 · DOI:10.1111/j.1600-6143.2007.02016.x

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.

MeSH Terms (17)

alpha-Galactosidase Animals Antigens, Surface CD59 Antigens Cells, Cultured Complement Activation Immunoglobulin G Mice Mice, Inbred C57BL Mice, Knockout Models, Animal Rats Rats, Inbred Lew Receptors, Cell Surface Transplantation, Heterologous Transplantation Tolerance Up-Regulation

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