Porcine endothelial cell activation in hDAF pig hearts transplanted in baboons with prolonged survival and lack of rejection.
Depletion of anti-alphaGal antibodies before and after transplantation with GAS 914, a polylysine containing alphaGal epitopes, together with immunosuppression, has been shown to prevent acute humoral xenograft rejection (AHXR) in hDAF pig-to-baboon xenotransplantation. This therapy was associated with low levels of serum anti-alphaGal antibodies and lack of antipig hemolytic antibodies (APA) during the entire transplant course. In the present study we investigated the condition of xenograft endothelial cells and the presence of other antipig antibodies. No xenograft failed because of AHXR. However, endothelial cell markers of activation, such as CD62, CD106, ET-1, and particularly 5A6/8, were detected at necropsy, along with a lack or scarce deposits of IgM and total absence of complement and fibrin. The endothelial cell markers were negative or slightly positive at biopsy obtained 30 minutes after transplantation. At the time of animal death serum xenoantibodies against pig aortic cells were also detected by immunochemistry whereas anti-alphaGal and APHA were almost absent, suggesting that the presence of non-anti-alphaGal and noncytotoxic xenoantibodies may cause endothelial activation.
Doménech
N
N
Research Unit, Hospital Juan Canalejo, La Coruña, Spain.
Diaz
T
T
Moscoso
I
I
Centeno
A
A
Lopez-Pelaez
E
E
Manez
R
R
D000208:Acute Disease; D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000097:blood; D018958:CD55 Antigens / Q000235:genetics*; D004730:Endothelium, Vascular / Q000276:immunology; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D010215:Papio; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
D015415:Biomarkers; D018958:CD55 Antigens; D007075:Immunoglobulin M