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, Gabriel Godman, David Stern, Giuseppe Andres

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1635-1649
Number of pages15
JournalAmerican Journal of Pathology
Volume155
Issue number5
DOIs
StatePublished - Jan 1 1999

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Papio
Anti-Idiotypic Antibodies
Swine
Heparan Sulfate Proteoglycans
Laminin
Antibodies
Basement Membrane
Heterografts
Extracellular Matrix
Fibroblasts
Griffonia
Heterophile Antibodies
Kidney
Heterologous Transplantation
Thyroglobulin
Vascular Endothelium
Transforming Growth Factors
Graft Survival
Allografts
Immunoglobulins

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Maruyama, S., Cantu, E., DeMartino, C., Wang, C. Y., Chen, J., Al-Mohanna, F., ... Andres, G. (1999). Interaction of baboon anti-α-galactosyl antibody with pig tissues. American Journal of Pathology, 155(5), 1635-1649. https://doi.org/10.1016/S0002-9440(10)65479-X

Interaction of baboon anti-α-galactosyl antibody with pig tissues. / Maruyama, Shoichi; Cantu, Edward; DeMartino, Cesare; Wang, Catherine Y.; Chen, Jonathan; Al-Mohanna, Futwan; Nakeeb, Shaheen M.; D'Agati, Vivette; Pernis, Benvenuto; Galili, Uri; Godman, Gabriel; Stern, David; Andres, Giuseppe.

In: American Journal of Pathology, Vol. 155, No. 5, 01.01.1999, p. 1635-1649.

Research output: Contribution to journalArticle

Maruyama, S, Cantu, E, DeMartino, C, Wang, CY, Chen, J, Al-Mohanna, F, Nakeeb, SM, D'Agati, V, Pernis, B, Galili, U, Godman, G, Stern, D & Andres, G 1999, 'Interaction of baboon anti-α-galactosyl antibody with pig tissues', American Journal of Pathology, vol. 155, no. 5, pp. 1635-1649. https://doi.org/10.1016/S0002-9440(10)65479-X
Maruyama S, Cantu E, DeMartino C, Wang CY, Chen J, Al-Mohanna F et al. Interaction of baboon anti-α-galactosyl antibody with pig tissues. American Journal of Pathology. 1999 Jan 1;155(5):1635-1649. https://doi.org/10.1016/S0002-9440(10)65479-X
Maruyama, Shoichi ; Cantu, Edward ; DeMartino, Cesare ; Wang, Catherine Y. ; Chen, Jonathan ; Al-Mohanna, Futwan ; Nakeeb, Shaheen M. ; D'Agati, Vivette ; Pernis, Benvenuto ; Galili, Uri ; Godman, Gabriel ; Stern, David ; Andres, Giuseppe. / Interaction of baboon anti-α-galactosyl antibody with pig tissues. In: American Journal of Pathology. 1999 ; Vol. 155, No. 5. pp. 1635-1649.
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