Effects of transfected complement regulatory proteins, MCP, DAF, and MCP/DAE hybrid, on complement-mediated swine endothelial cell lysis

Transplantation. 1994 Oct 15;58(7):834-40.

Abstract

We established several swine endothelial cell (SEC) lines, expressing human MCP (CD46), DAF (CD55), and MCP/DAF hybrid by transfection of cDNA, and assessed the function of these transfectant molecules on complement-mediated cell lysis as an in vitro hyperacute rejection model of swine to human discordant xenograft. Discordant organ xenografts are hyperacutely rejected by complement activation. Amelioration of complement-mediated lysis by these transfectant molecules was tested in each SEC line by lactate dehydrogenase assay. Naive swine endothelial cells were markedly damaged by human complement mainly via the classical pathway, activating only minimally the alternative pathway of human complement. Both MCP and DAF protected SEC from human complement attack in parallel with the expression density, with DAF being more effective than MCP. The MCP/DAF hybrid was more effective than MCP alone, and as effective as DAF in this system. The results suggest that the transfection of DAF or the MCP/DAF hybrid cDNA into organs to be transplanted could protect against hyperacute rejection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • CD55 Antigens
  • Cells, Cultured
  • Complement Activation*
  • Complement Inactivator Proteins / genetics
  • Complement Inactivator Proteins / immunology*
  • Cytotoxicity, Immunologic*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology*
  • Hybrid Cells
  • L-Lactate Dehydrogenase / metabolism
  • Membrane Cofactor Protein
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Swine
  • Transfection

Substances

  • Antigens, CD
  • CD55 Antigens
  • Complement Inactivator Proteins
  • Membrane Cofactor Protein
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • L-Lactate Dehydrogenase