Mechanism of delayed rejection in transgenic pig-to-primate cardiac xenotransplantation.
J Surg Res
; 90(2): 119-25, 2000 May 15.
Article
em En
| MEDLINE
| ID: mdl-10792951
ABSTRACT
BACKGROUND:
Pig-to-primate cardiac xenografts undergo hyperacute rejection (HAR), in which primate IgM bind to porcine endothelial alpha-Gal molecules and activate membrane attack complex (MAC) deposition. Prolonged graft survival can be achieved by using transgenic pig donors, which express human complement regulatory proteins (hCRP) to inhibit MAC. However, these xenografts invariably fail from delayed xenograft rejection (DXR). We sought to investigate the poorly understood DXR process. MATERIALS ANDMETHODS:
Wild-type (n = 3) and transgenic (n = 3) porcine hearts were heterotopically transplanted into baboons. Biopsies were analyzed by histology and by immunohistochemistry for porcine endothelial markers (vWF, alpha-Gal, and beta-Gal) and primate IgM and MAC deposition.RESULTS:
Wild-type xenografts survived 60-80 min but succumbed to rapid IgM/MAC deposition and microvascular thrombosis. Transgenic xenografts avoided HAR but showed increasing IgM/MAC deposition before rejection on days 5, 7, and 11. Serum from baboons after transgenic xenograft rejection showed increased activity against porcine endothelial cells, and in vitro incubation of untransplanted porcine cardiac sections with sensitized baboon serum showed elevated microvascular IgM binding. Increased IgM deposition appeared specific to alpha-Gal, since it competes specifically with alpha-Gal-specific GS-4 lectin, but not with beta-Gal-specific RCA-1 lectin. Competition with GS-4 was not seen if naïve baboon serum was used.CONCLUSION:
DXR may be mediated by increasing baboon IgM binding on porcine microvascular endothelial alpha-Gal molecules.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante Heterólogo
/
Transplante de Coração
/
Lectinas de Plantas
/
Rejeição de Enxerto
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Surg Res
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos