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Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury

Nature Medicine volume 1, pages 423–427 (1995)Cite this article

Abstract

The susceptibility of xenografts to hyperacute rejection is postulated to reflect in part failure of complement regulatory proteins (CRPs) to control activation of heterologous complement on graft endothelium. To test this concept, transgenic swine expressing the human CRP decay accelerating factor and CD59 were developed using a novel expression system involving transfer of the proteins from erythrocytes to endothelial cells. Hearts from transgenic swine transplanted into baboons had markedly less vascular injury and functioned for prolonged periods compared to hearts from nontransgenic swine. These results indicate that expression of human CRPs in xenogeneic organs may contribute to successful xenografting and suggest that intercellular protein transfer might be a useful approach for expression of heterologous proteins in endothelial cells.

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Authors and Affiliations

  1. Department of Surgery, Medical Sciences Research Building, Duke University Medical Center, Box 2605, Durham, North Carolina, 27710, USA

    Kenneth R. McCurry, Cristobal G. Alvarado, Adrian H. Cotterell & Jeffrey L. Platt

  2. Departments of Pediatrics and Immunology, Medical Sciences Research Building, Duke University Medical Center, Box 2605, Durham, North Carolina, 27710, USA

    Jeffrey L. Platt

  3. Nextran, 303B College Road East, Princeton, New Jersey, 08540, USA

    David L. Kooyman, Michael J. Martin & John S. Logan

Authors
  1. Kenneth R. McCurry
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  2. David L. Kooyman
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  4. Adrian H. Cotterell
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  5. Michael J. Martin
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  6. John S. Logan
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  7. Jeffrey L. Platt
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McCurry, K., Kooyman, D., Alvarado, C. et al. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. Nat Med 1, 423–427 (1995). https://doi.org/10.1038/nm0595-423

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