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

J. Wen Ding, T. Zhou, L. Ma, D. Yin, J. Shen, C. P.Y. Ding, I. Y. Tang, G. W. Byrne, A. S. Chong

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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-α-Gal IgG1. The accommodated grafts survived a bolus dose of anti-α-Gal IgG1, while freshly transplanted second grafts were rejected. To study the mechanism of anti-α-Gal IgG1-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-α-Gal IgG1 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.

Original languageEnglish (US)
Pages (from-to)32-40
Number of pages9
JournalAmerican Journal of Transplantation
Volume8
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Keywords

  • Accommodation
  • Complement regulatory proteins
  • Endothelial cells
  • Monoclonal antibodies
  • Xenograft
  • α-Gal

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