
Characterization of porcine endothelial cell determinants recognized by human natural antibodies
Abstract: Organs transplanted from pigs to primates are subject to hyperacute rejection. This immunologic reaction is initiated by the recipient's natural antibodies that bind to endothelial cell antigens of the organ, resulting in the activation of the complement system and rapid destruction of the graft. Various lines of evidence, particularly blocking studies, using purified carbohydrates have suggested that the endothelial cell determinant recognized by human natural antibodies is a terminal galactose in an α configuration (α‐Gal). Although these studies are compelling, they fall short of proof because xenoreactive natural antibodies, being polyreactive, might bind to structures other than those used for blocking. Moreover, in vivo evidence that anti‐α‐Gal antibodies participate in hyperacute rejection has not been reported. Here we report that an enzyme specific for α‐Gal, α‐galactosidase, removes α‐galactose residues from both intact porcine aortic endothelial cells and immobilized porcine aortic endothelial cell membrane extracts and that as a result of this, xenoreactive natural antibody binding is lowered by 70 to 80%. This decrease in binding of human IgM causes a corresponding decrease in complement activation. Similar results were obtained using the sera of other Old World primates. Digestion of immobilized porcine aortic endothelial cell membrane extracts with α‐galactosidase produced a similar reduction in human IgM binding to gp 115/135. These results indicate that a terminal α‐galactose is an important component of the gp 115/135 porcine endothelial cell antigen. We also report that perfusion of porcine organs I with primate serum removes anti‐α‐Gal IgM from the serum. © 1994 Munksgaard
Duke Scholars
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- Surgery
- 3202 Clinical sciences
- 1103 Clinical Sciences
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Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Surgery
- 3202 Clinical sciences
- 1103 Clinical Sciences