Expression of human decay accelerating factor (hDAF) in transgenic pigs regulates complement activation during ex vivo liver perfusion — immunopathological findings

  • A. Pascher
  • Ch. Poehlein
  • M. Storck
  • D. Abendroth
  • J. Mueller-Hoecker
  • V. K. Young
  • W. Koenig
  • D. J. G. White
  • C. Hammer
Conference paper

Abstract

Ex vivo perfusions of human decay accelerating factor-expressing transgenic (n = 3), and nontransgenic (n = 6) porcine livers with human blood revealed a higher degree of organ damage in nontransgenic pig livers. Transgenic livers were protected from immunohistologically detectable complement deposition, despite corresponding IgM and IgG deposits in both groups. Complement activation and consumption of C3 and C4 turned out to be lower in transgenic pig livers. In contrast to livers of normal landrace pigs, livers from genetically manipulated pigs showed no morphological alterations after perfusion.

Key words

Decay accelerating factor Transgenic pig Ex vivo perfusion Immunohistology Complement 

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References

  1. 1.
    Baldwin WM III, Pruitt SK, Brauer RB, et al (1995) Complement in organ transplantation — contributions to inflammation, injury and rejection. Transplantation 59: 797–808PubMedGoogle Scholar
  2. 2.
    Burdick JF, Fair JH (1994) Xenoperfusion: the pig liver as a bridge. Xeno 2: 3–5Google Scholar
  3. 3.
    Carrington CA, Richards AC, Cozzi E, et al (1995) Expression of human DAF and MCP on pig endothelial cells protects from human complement. Transplant Proc 27: 321–323PubMedGoogle Scholar
  4. 4.
    Chari RS, Collins BH, Magee JC, et al (1994) Treatment of hepatic failure with ex vivo pig liver perfusion followed by liver transplantation. N Engl J Med 331: 234–237PubMedCrossRefGoogle Scholar
  5. 5.
    Cozzi E, Langford GA, Wright L, et al (1995) Comparative analysis of human DAF expression in the tissues of trans-genic pigs and man. Transplant Proc 27: 319–320PubMedGoogle Scholar
  6. 6.
    Makowka L, Cramer DV, Hoffman A, et al (1995) The use of a pig liver xenograft for temporary support of a patient with fulminant hepatic failure. Transplantation 59: 1654–1659CrossRefGoogle Scholar
  7. 7.
    McKenzie IFC, Koulmanda M, Mandel T, et al (1995) Comparative studies of the major xenoantigen gala(1,3)gal in pigs and mice. Transplant Proc 27: 247–248PubMedGoogle Scholar
  8. 8.
    Neuhaus P, Blumhardt G (1993) Extracorporeal liver perfusion: applications of an improved model for experimental studies of the liver. Int J Artif Organs 16: 729–739PubMedGoogle Scholar
  9. 9.
    Rosengard AM, Cary NRB, Langford GA, et al (1995) Tissue expression of human complement inhibitor, decay accelerating factor, in transgenic pigs — a potential approach for preventing xenograft rejection. Transplantation 59: 1325–1333PubMedGoogle Scholar
  10. 10.
    Schön MR, Lemmens HP, Neuhaus P, et al (1994) Improved xenogeneic extracorporeal liver perfusion. Transplant Proc 26: 1293–1297PubMedGoogle Scholar
  11. 11.
    Yannoutsos N, Langford GA, Cozzi E et al (1995) Production of pigs trans-genic for human regulators of complement activation. Transplant Proc 27: 324–325PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • A. Pascher
    • 1
  • Ch. Poehlein
    • 1
  • M. Storck
    • 2
  • D. Abendroth
    • 2
  • J. Mueller-Hoecker
    • 3
  • V. K. Young
    • 4
  • W. Koenig
    • 5
  • D. J. G. White
    • 5
  • C. Hammer
    • 1
  1. 1.Institute for Surgical Research, Klinikum GrosshadernLMU MunichMunichGermany
  2. 2.Department of Surgery IIUniversity of UlmGermany
  3. 3.Institute for Pathology, Klinikum GrosshadernLMU MunichGermany
  4. 4.Department of Cardiothoracic SurgeryPapworth HospitalCambridgeUK
  5. 5.Department of SurgeryUniversity of CambridgeUK

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