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Interaction of Baboon Anti-α-Galactosyl Antibody with Pig Tissues
Journal article   Open access   Peer reviewed

Interaction of Baboon Anti-α-Galactosyl Antibody with Pig Tissues

Shoichi Maruyama, Edward Cantu, Cesare DeMartino, Catherine Y. Wang, Jonathan Chen, Futwan Al-Mohanna, Shaheen M. Nakeeb, Vivette D’Agati, Benvenuto Pernis, Uri Galili, …
The American journal of pathology, v 155(5), pp 1635-1649
01 Nov 1999
DOI: https://doi.org/10.1016/S0002-9440(10)65479-X
PMID: 10550320
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/s0002-9440(10)65479-xView
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open
url
https://doi.org/10.1016/S0002-9440(10)65479-XView
Published, Version of Record (VoR) Open

Abstract

Regular
As barriers to xenotransplantation are surmounted, such as suppression of hyperacute rejection allowing improved graft survival, it becomes important to define longer-term host-xenograft interactions. To this end we have prepared in baboons high titer anti-α-Galactosyl (αGal) and anti-porcine aortic endothelial cell antibodies, similar to human natural xenoantibodies and reactive with epitopes of thyroglobulin, laminin, and heparan sulfate proteoglycans. When injected into pigs with a protocol similar to that used in the rat to show the nephritogenic potential of heterologous anti-laminin and anti-heparan sulfate proteoglycan antibodies, baboon immunoglobulins bound first to renal vascular endothelium, and later to interstitial cells, especially fibroblasts and macrophages, and to antigens in basement membranes and extracellular matrix, where they colocalized with laminin- and heparan sulfate proteoglycan-antibodies, and with bound Griffonia simplicifolia B4. A similar binding was observed in other organs. The pigs did not develop an acute complement-dependent inflammation, but rather chronic lesions of the basement membranes and the extracellular matrix. Incubation of renal fibroblasts with baboon anti-α-Galactosyl antibodies resulted in increased synthesis of transforming growth factor-β and collagen, suggesting a possible basis for the fibrotic response. The results demonstrate that in this experimental model a consequence of αGal antibody interaction with porcine tissues, is immunoreactivity with αGal on matrix molecules and interstitial cells, priming mechanisms leading to fibrosis resembling that in chronic allograft rejection. The possibility that similar lesions may develop in long-surviving pig xenografts is discussed.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Pathology
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