Expression of Human CD46 Modulates Inflammation Associated With GalTKO Lung Xenograft Injury

Expression of Human CD46 Modulates Inflammation Associated With GalTKO Lung Xenograft Injury

Evaluation of lungs from GalTKO.hCD46 pigs, genetically modified to lack the galactose‐α(1,3)‐galactose epitope (GalTKO) and to express human CD46, a complement regulatory protein, has not previously been described. Physiologic, hematologic and biochemical parameters during perfusion with heparinize...

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Veröffentlicht in:American journal of transplantation 2014-05, Vol.14 (5), p.1084-1095
Hauptverfasser: Burdorf, L., Stoddard, T., Zhang, T., Rybak, E., Riner, A., Avon, C., Laaris, A., Cheng, X., Sievert, E., Braileanu, G., Newton, A., Phelps, C. J., Ayares, D., Azimzadeh, A. M., Pierson, R. N.
Format: Artikel
Sprache:eng
Schlagworte:
Animals
Animals, Genetically Modified
Blood Coagulation - immunology
CD55 Antigens - genetics
Coagulation
complement
Complement Activation - immunology
Epitopes - immunology
ex vivo perfusion
Galactosyltransferases - physiology
GalTKO.hCD46
Graft Survival - physiology
Histamine - metabolism
Humans
Immunoenzyme Techniques
Inflammation - immunology
Inflammation - metabolism
Inflammation - pathology
leukocyte adhesion
lung
Lung Injury - immunology
Lung Injury - pathology
Lung Injury - surgery
Lung Transplantation
Neutrophils - metabolism
platelet activation
Swine
Swine, Miniature
Transplantation, Heterologous
xenotransplantation
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Zusammenfassung:Evaluation of lungs from GalTKO.hCD46 pigs, genetically modified to lack the galactose‐α(1,3)‐galactose epitope (GalTKO) and to express human CD46, a complement regulatory protein, has not previously been described. Physiologic, hematologic and biochemical parameters during perfusion with heparinized fresh human blood were measured for 33 GalTKO.hCD46, GalTKO (n = 16), and WT pig lungs (n = 16), and 12 pig lungs perfused with autologous pig blood. Median GalTKO.hCD46 lung survival was 171 min compared to 120 for GalTKO (p = 0.27) and 10 for WT lungs (p 
ISSN:1600-6135
1600-6143
DOI:10.1111/ajt.12673