Summary
The targets of preformed natural antibodies need to be identified whenever the use of pig organs is considered for human transplantation. In this study we used extracorporeal perfusion of pig organs with human blood, immunocytological techniques and immuno-electron microscopy to identify the targets and the nature of human preformed natural antibodies against pig antigens. The antibodies were found to be mainly of the IgG and IgM type and directed not only against endothelial cells, but also against mesenchymal and epithelial structures. To reproduce an in vivo situation, a Bio-pump was used to xenoperfuse pig kidneys and livers with human fresh oxygenated blood at 37°C, drawn from polycythaemic patients. Biopsies showed a deposition of human IgG and IgM on tubuli and glomeruli of pig kidneys and on endothelial cells of pig livers. Preperfusion of pig liver with human blood for 45 minutes before perfusion of kidneys significantly reduced the deposition of the natural antibodies.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ackerman, G. A., Yang, J. & Wolken, K. W. (1983) Differential surface labeling and internalization of glucagon by peripheral leukocytes. J. Histochem. Cytochem. 31, 433–40.
Alexandre, G. P. J., Gianello, P. & Latinne, D. (1989) Plasmapheresis and splenectomy in experimental renal xenotransplantation. In Xenograft 25 (edited by Hardy, M. A.), p. 259. New York: Elsevier Science.
Archimbaud, E., Islam, A. & Preisler, H. D. (1987) Immunoperoxidase detection of myeloid antigen in glycomethacrylate-embedded human bone marrow. J. Histochem. Cytochem. 35, 595–9.
Auchincloss, H. J. R. (1988) Xenogenic transplantation. Transplantation 46, 1–20.
Bach, F. H. & Platt, J. L. (1992) Xenotransplantation: a view of issues. Transplant. Proc. 24, 49–52.
Barker, C. F. & Markmann, J. F. (1992) Xenografts: is there a future? Surgery 112, 3–5.
Beckstead, J. H. (1983) The evaluation of human lymph nodes, using plastic sections and enzyme histochemistry. Am. J. Clin. Pathol. 80, 131–7.
Beckstead, J. H., Halverson, P. S., Ries, C. A. & Bainton, D. F. (1981) Enzyme histochemistry on biopsy specimens of pathologic human bone marrow. Blood 57, 1088–98.
Carlemalm, E., Garavito, R. M. & Villiger, W. (1982) Resin development for electron microscopy and an analysis of embedding at low temperature. J. Microsc. 126, 123–43.
Casey, T. T., Cousar, J. B. & Collins, R. D. (1988) A simplified plastic embedding and immunohistologic technique for immuno-phenotypic analysis of human hematopoietic and lymphoid tissues. Amer. J. Pathol. 131, 183–9.
Cooper, D. K. C., Human, P. A. & Lexer, G. (1988) Effects of cyclosporine and antibody adsorption on pig cardiac xenograft survival in the baboon. J. Heart. Transplant. 7, 2238–46.
Cooper, D. K. C., Kemp, E., Reemtsma, K. & White, D. J. G. (eds) (1991) Xenotransplantation. The ransplantation of organs and times between species. Berlin: Springer-Verlag.
Cramer, D. V., Chapman, F. A., Jaffe, B. D. & Makowa, L. (1992) The prolongation of concordant hamster-to-rat cardiac xenografts by brequinar sodium. Transplantation 54, 403–7.
Danscher, G. & Norgaard, J. O. R. (1983) Light microscopic visualization of colloidal gold on resin-embedded tissue. J. Histochem. Cytochem. 31, 1394–8.
Hammer, C., Chaussy, C. & Brendel, W. (1972) Preformed natural antibodies in animals and man. Eur. Surg. Res. 5, 162–6.
Hsu, Y. H. (1984) Immunogold for detection of antigen on nitrocellulose paper. Anal. Biochem. 242, 221–5.
Hsu, S., Raine, L. & Fanger, H. (1981) Use of avidinbiotin-peroxidase complex (ABC) in immunoperoxidase techniques. J. Histochem. Cytochem. 29, 577–80.
Kahan, B. D. (1983) Cyclosporine: biological activity and clinical application. Transplant Proc. 15 (suppl 1–2), 2211–12.
Kellenberger, E., Carlemalm, E., Villiger, W., Roth, J. & Garavito, M. (1980) Low denaturation embedding for electron microscopy of thin sections. Waldkraiburg, Germany, Chemish Werke Lowi GmbH.
Kemp, E., Kemp, G., Jacobseen, A. & Lundborg, C. J. (1977) Prolongation of survival of renal xenografts by infusion of donor blood. Acta Path. Microbiol. Scand. 85, 267–301.
Marino, I. R., Ferla, G., Celli, S., Stieber, A., Muttillo, L., Maggiano, N., Mazzaferro, V., Perrelli, L. & Musiani, P. (1990) Hyperacute rejection of renal discordant xenograft (pig-to-rabbit): model assessment and rejection mechanisms. Transplant Proc. 22, 1071–6.
Otte, K. E., Andersen, N., Jorgensen, K. A., Ristensen, K., Barfort, P., Starclint, H., Larsen, S. & Kemp, E. (1990) Xenoperfusion of pig kidney with human ABO whole blood. Transplant Proc. 22, 1091–3.
Platt, J. L., Vercellotti, G. M., Dalmasso, A. P., Matas, A. J., Bolman, R. M., Najarian, J. S. & Bach, F. H. (1990a) Transplantation of discordant xenograft: a review progress. Immunol. Today 11, 450–7.
Platt, J. L., Lindman, B. J., Chen, H., Spitalnick, S. L. & Bach, F. H. (1990b) Endothelial cell antigens recognized by xeno-reactive human natural antibodies. Transplantation 50, 817–22.
Platt, J. L., Fischel, R. J., Matas, A. J., Reif, S. A., Bolman, R. M. & Bach, F. H. (1991) Immunopathology of hyperacute rejection in a swine-to-primate model. Transplantation 52, 214–20.
Pozzetto, U., Citterio, F., Caizzi, M. P., Severino, F. & Castagneto, M. (1990) Umoral immune reactions to pig antigens in human. Transplant Proc. 22, 2000–1.
Scott Clark, D., Foker, J. E., Pickering, R., Good, R. A. & Varco, R. L. (1966) Evidence for two platelet populations in xenograft rejection. Surg. Forum 17, 264–70.
Starzl, T. E., Todo, S., Fung, J., Demetris, A. J., Venkatara-Manan, R. & Jain, A. (1989) FK 506 for human liver, kidney and pancreas transplantation. Lancet 2, 1000–5.
Starzl, T. E., Fung, J., Tzakis, A., Todo, S., Demetris, A. J., Marino, I. R., Doyle, H., Zeevi, A., Warty, V., Michaels, M., Kusne, S., Rudert, W. A. & Trucco, M. (1993) Baboon-to-human liver transplantation. Lancet 341, 65–71.
Terasaki, P. J. (1993) Clinical Transplants. Los Angeles: UCLA Tissue typing Laboratory.
Tixier, D., Levy, C., LeBourgeois, J. P., Leandri, J. & Loisance, D. (1992) Xenogreffes cardiaques discordandantes. Presse Med. 21, 1941–4.
Transplant Council Of Europe. (1993) Vol 5. Foundation Marcel Merieux.
VanGoor, H., Harms, G., Gerrits, P. O., Kroese, G. M., Poppema, S. & Groud, J. (1988) Immunohistochemical antigen demonstration in plastic-embedded lymphoid tissue. J. Histochem. Cytochem. 36, 115–20.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Maggiano, N., Citterio, F., Evangelista, A. et al. Immunomicroscopical localization of human preformed natural antibodies against pig tissues in xenogeneic transplantation. Histochem J 26, 553–562 (1994). https://doi.org/10.1007/BF00158589
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00158589