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Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection
Author(s) -
Nguyen BaoNgoc H.,
Azimzadeh Agnes M.,
Schroeder Carsten,
Buddensick Thomas,
Zhang Tianshu,
Laaris Amal,
Cochrane Megan,
Schuurman HenkJan,
Sachs David H.,
Allan James S.,
Pierson III Richard N.
Publication year - 2011
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2011.00633.x
Subject(s) - xenotransplantation , ex vivo , platelet , lung , epitope , complement system , in vivo , peritubular capillaries , pathology , immunology , medicine , transplantation , antibody , andrology , biology , microbiology and biotechnology
Nguyen B‐NH, Azimzadeh AM, Schroeder C, Buddensick T, Zhang T, Laaris A, Cochrane M, Schuurman H‐J, Sachs DH, Allan JS, Pierson RN. Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection. Xenotransplantation 2011; 18: 94–107. © 2011 John Wiley & Sons A/S. 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.