title: Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection.
abstract: BACKGROUND
  Galactosyl transferase gene knock-out (GalTKO) swine offer a unique tool to evaluate the role of the Gal antigen in xenogenic lung hyperacute rejection.
  
  
  METHODS
  We perfused GalTKO miniature swine lungs with human blood. Results were compared with those from previous studies using wild-type and human decay-accelerating factor-transgenic (hDAF(+/+) ) pig lungs.
  
  
  RESULTS
  GalTKO lungs survived 132 ± 52 min compared to 10 ± 9 min for wild-type lungs (P = 0.001) and 45 ± 60 min for hDAF(+/+) lungs (P = 0.18). GalTKO lungs displayed stable physiologic flow and pulmonary vascular resistance (PVR) until shortly before graft demise, similar to autologous perfusion, and unlike wild-type or hDAF(+/+) lungs. Early (15 and 60 min) complement (C3a) and platelet activation and intrapulmonary platelet deposition were significantly diminished in GalTKO lungs relative to wild-type or hDAF(+/+) lungs. However, GalTKO lungs adsorbed cytotoxic anti-non-Gal antibody and elaborated high levels of thrombin; their demise was associated with increased PVR, capillary congestion, intravascular thrombi and strong CD41 deposition not seen at earlier time points.
  
  
  CONCLUSIONS
  In summary, GalTKO lungs are substantially protected from injury but, in addition to anti-non-Gal antibody and complement, platelet adhesion and non-physiologic intravascular coagulation contribute to Gal-independent lung injury mechanisms.
authors.affiliation: Department of Surgery, University of Maryland and Baltimore VAMC, Baltimore, MD 21201, USA.
authors.forename: Bao-Ngoc H
authors.initials: BN
authors.lastname: Nguyen
authors.forename: Agnes M
authors.initials: AM
authors.lastname: Azimzadeh
authors.forename: Carsten
authors.initials: C
authors.lastname: Schroeder
authors.forename: Thomas
authors.initials: T
authors.lastname: Buddensick
authors.forename: Tianshu
authors.initials: T
authors.lastname: Zhang
authors.forename: Amal
authors.initials: A
authors.lastname: Laaris
authors.forename: Megan
authors.initials: M
authors.lastname: Cochrane
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Schuurman
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: James S
authors.initials: JS
authors.lastname: Allan
authors.forename: Richard N
authors.initials: RN
authors.lastname: Pierson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000906:Antibodies / Q000097:blood; D018958:CD55 Antigens / Q000235:genetics; D016207:Cytokines / Q000097:blood; D000939:Epitopes / Q000235:genetics*; D005700:Galactosyltransferases / Q000235:genetics*; D055786:Gene Knockout Techniques; D006084:Graft Rejection / Q000235:genetics / Q000503:physiopathology*; D006085:Graft Survival / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016040:Lung Transplantation / Q000502:physiology*; D010477:Perfusion; D013552:Swine; D013556:Swine, Miniature; D014183:Transplantation, Heterologous / Q000502:physiology*
chemical_list: D000906:Antibodies; D018958:CD55 Antigens; D016207:Cytokines; D000939:Epitopes; D005700:Galactosyltransferases; C530267:alpha-1,3-galactosyltransferase 1, porcine