title: High-level endothelial expression of human CD59 prolongs heart function in an ex vivo model of xenograft rejection.
abstract: BACKGROUND
  Hyperacute rejection of discordant xenografts is dependent on activation of the complement system of the recipient. Transgenic expression of recipient complement regulatory factors in donor tissue has proved to be a promising approach to dealing with hyperacute rejection, although the relationship between the level of complement regulatory factor expression and the degree of protection is not well established. Here, we examine this relationship using CD59 transgenic mouse hearts in an ex vivo model of xenograft rejection.
  
  
  METHODS
  The level of expression of CD59 in two lines of transgenic mice, in which CD59 is expressed under the control of either the murine H2Kb (MHC class I) promoter (line CA-17) or the endothelium-specific human intercellular adhesion molecule-2 promoter (line 237-7), was compared by immunohistochemistry and flow cytometry. Hearts from both groups and wild-type controls were perfused ex vivo with human plasma, and mean heart work for each group was compared over a 60-min period.
  
  
  RESULTS
  CD59 expression on cardiac endothelial cells isolated from homozygous CA-17 mice was 25- to 30-fold lower than that on cardiac endothelial cells from heterozygous 237-7 mice. CA-17 hearts perfused with 6% human plasma exhibited a reduction in deposition of the membrane attack complex, but not a prolongation of function, compared with nontransgenic mouse hearts. In contrast, 237-7 hearts showed significantly prolonged function during perfusion with 20% plasma.
  
  
  CONCLUSIONS
  High-level endothelial-specific expression of CD59 was effective in prolonging the function of mouse hearts perfused with 20% human plasma, whereas low-level, broader expression did not provide protection from 6% plasma.
authors.affiliation: Immunology Research Centre, St. Vincent's Hospital, Fitzroy, Victoria, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Cowan
authors.forename: C A
authors.initials: CA
authors.lastname: Somerville
authors.forename: T A
authors.initials: TA
authors.lastname: Shinkel
authors.forename: M
authors.initials: M
authors.lastname: Katerelos
authors.forename: A
authors.initials: A
authors.lastname: Aminian
authors.forename: M
authors.initials: M
authors.lastname: Romanella
authors.forename: M J
authors.initials: MJ
authors.lastname: Tange
authors.forename: M J
authors.initials: MJ
authors.lastname: Pearse
authors.forename: A J
authors.initials: AJ
authors.lastname: d'Apice
mesh_terms: D000818:Animals; D018957:CD59 Antigens / Q000378:metabolism*; D015932:Complement C3c / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology*; D006084:Graft Rejection; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010477:Perfusion; D014183:Transplantation, Heterologous
chemical_list: D018957:CD59 Antigens; D003186:Complement C9; D015932:Complement C3c