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Immunofluorescent localization of pig complement component 3, regardless of the presence or absence of detectable immunoglobulins, in hyperacutely rejected heart xenografts

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Summary

Rabbit heart xenografts transplanted into the neck of newborn pigs were all hyperacutely rejected within two hours regardless of the presence or absence of detectable endogenous immunoglobulins (Ig). Cryostat tissue sections were prepared from the rejected rabbit hearts and incubated with sheep polyclonal antibodies against pig complement component 3 (C3), pig IgG and pig IgM. Specific immunoreaction was visualized by fluorescein-conjugated antibodies to sheep IgG. C3 was localized mainly on the surfaces of vascular endothelial as well as myocardial cells, and the localization was not dependent upon the presence of pig immunoglobulins within the same tissue. Both pig IgG and IgM were detected only in the heart xenografts transplanted into suckled pigs, whereas no trace of immunoglobulin was found in those transplanted into circulating antibody-free presuckled pigs. Treatment with cobra venom factor (which inhibits complement activity) prior to transplantation prolonged xenograft survival and completely abolished C3 immunostaining. The results provide new evidence at the histochemical level that the alternative pathway of complement is involved in hyperacute xenograft rejection of the species combination (rabbit to pig) used in this study.

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References

  • Adachi, H., Rosengard, B. R., Hutchins, G. M., Hall T. S., Baumgartner, W. A., Borkon, A. M. &Reitz, B. A. (1987) Effects of cyclosporine, aspirin, and contra venom factor on discordant cardiac xenograft survival in rats.Transplant. Proc. 19, 1145–8.

    Google Scholar 

  • Auchincloss, H. Jr. (1988) Xenogeneic transplantation. A review.Transplantation 46, 1–20.

    Google Scholar 

  • Auchincloss, H. Jr (1990) Comment by Hugh Auchincloss Jr.Immunol. Today 11, 456–7.

    Google Scholar 

  • Berden, J. H., Bogman, M. J., Hagemann, F. H., Tamboer, W. P. &Koene, R. A. (1981) Complement-dependent and independent mechanisms in acute antibody-mediated rejection of skin xenografts in the mouse.Transplantation 32, 265–70.

    Google Scholar 

  • Brambell, F. W. R. (1958) Pre-natal transference of antibodies.Vet. Rec. 70, 1060–3.

    Google Scholar 

  • Cairns, T. D. H., Taube, D. H., Stevens, N., Binns, R. &Welsh, K. I. (1991) Xenografts-future prospects for clinical transplantation.Immunol. Lett. 29, 167–70.

    Google Scholar 

  • Calne, R. Y. (1970) Organ transplantation between widely disparate species.Transplant. Proc. 2, 550–6.

    Google Scholar 

  • Calne, R. Y. (1989) Xenograft: functional definition. InXenograft 25 (edited byHardy, M. A.) pp. 3–6. Amsterdam: Elsevier Science Publishers.

    Google Scholar 

  • Cochrane, C. G., Müller-Eberhard, H. J. &Aikin, B. S. (1970) Depletion of plasma complementin vivo by a protein of cobra venom: its effect on various immunologic reactions.J. Immunol. 105, 55–69.

    Google Scholar 

  • Fischel, R. J., Bolman, R. M. III, Platt, J. L., Najarian, J. S., Bach, F. H. &Matas, A. J. (1990) Removal of IgM anti-endothelial antibodies results in prolonged cardiac xenograft survival.Transplant. Proc. 22, 1077–8.

    Google Scholar 

  • Forbes, R. D. C. &Guttmann, R. D. (1989) Histopathology and mechanisms of rejection in xenotransplantation. InXenograft 25 (edited byHardy, M. A.) pp. 133–47. Amsterdam: Elsevier Science Publishers.

    Google Scholar 

  • Gewurz, H., Clark, D. S., Cooper, M. D., Varco, R. L. &Good, R. A. (1967) Effect of cobra venom-induced inhibition of complement activity on allograft and xenograft rejection reactions.Transplantation 5, 1296–303.

    Google Scholar 

  • Haisch, C. E., Lodge, P. A., Huber, S. A. &Thomas, F. T. (1990) The vascular endothelial cell is central to xenogeneic immune reactivity.Surgery 108, 306–11.

    Google Scholar 

  • Henry, M. L., Han, L. K., Davies, E. A., Orosz, C. G., Sedmak, D. D. &Ferguson, R. M. (1989) The role of organ perfusion in xenotransplantation: influence ofex vivo xenoantibody adsorption on xenograft survival. InXenograft 25 (edited byHardy, M. A.) pp. 249–57. Amsterdam: Elsevier Science Publishers.

    Google Scholar 

  • Hudson, L. &Hay, F. C. (1989) InPractical Immunology. 3rd edn. pp. 266–7. Oxford: Blackwell Scientific Publications.

    Google Scholar 

  • Johnston, P. S., Lim, S. M. L., Wang, M.-W., Wright, L. &White, D. J. G. (1991) Hyperacute rejection of xenografts in the complete absence of antibody.Transplant. Proc. 23, 877–9.

    Google Scholar 

  • Johnston, P. S., Wang, M.-W., Lim, S. M. L., Wright, L. J. & White, D. J. G. (1992) Discordant xenograft rejection in an antibody free model.Transplantation (in press).

  • Kemp, E., White, D., Dieperink, H., Larsen, S., Starklint, H. &Steinbruchel, D. (1987) Delayed rejection of rabbit kidneys transplanted into baby pigs.Transplant. Proc. 19, 1143–4.

    Google Scholar 

  • Kux, M. (1975) Hyperacute kidney graft rejection with and without demonstration of antibodies.Chirurg. 46, 262–7.

    Google Scholar 

  • Lambris, J. D. (1988) The multifunctional role of C3, the third component of complement.Immunol. Today 9, 387–93.

    Google Scholar 

  • Lexer, G., Cooper, D. K. C., Rose, A. G., Wicomb, W. N., Rees, J., Keraan, M. &Du Toit, E. (1986) Hyperacute rejection in a discordant (pig to baboon) cardiac xenograft model.J. Heart Transplant. 5, 411–8.

    Google Scholar 

  • Locke, R. F., Segre, D. &Myres, W. L. (1964) The immunologic behavior of baby pigs. IV. Intestinal absorption and persistence of 6.6S and 18S antibodies of ovine origin and their role in the immunologic competence of baby pigs.J. Immunol. 93, 576–83.

    Google Scholar 

  • Mancini, G., Vaerman, J.-P., Carbonara, A. O. &Heremans, J. F. (1964) A single-radial-diffusion method for the immunological quantitation of proteins.Protides Biol. Fluids 11, 370–3.

    Google Scholar 

  • Marino, I. R., Ferla, G., Celli, S., Stieber, A., Muttillo, I., 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.

    Google Scholar 

  • Mejía-Laguna, J. E., Martínez-Palomo, A., Biro, C. E., Chávez, B., López-Soriano, F. &García-Cornejo, M. (1972) Morphologic study of the participation of the complement system in hyperacute rejection of renal xenotransplants.Am. J. Pathol. 69, 71–8.

    Google Scholar 

  • Milgrom, F. (1989) Natural antibodies and xenograft rejection. InXenograft 25 (edited byHardy, M. A.) pp. 149–57. Amsterdam: Elsevier Science Publishers.

    Google Scholar 

  • Miyagawa, S., Hirose, H., Shirakura, R., Naka, Y., Nakata, S., Kawashima, Y., Seya, T., Matsumoto, M., Uenaka, A. &Kitamura, H. (1988) The mechanism of discordant xenograft rejection.Transplantation 46, 825–30.

    Google Scholar 

  • Miyagawa, S., Hirose, H., Shirakura, R., Nakata, S., Naka, Y., Kitagawa, S., Nakano, S., Matsumoto, M., Seya, T. &Kitamura, H. (1989) The mechanism of discordant xenograft rejection.Transplant. Proc. 21, 520–1.

    Google Scholar 

  • O'regan, C. C., Robitaille, P., Pinto-Blonde, M. &Chartrand, C. (1979) Delayed rejection of cardiac xenografts in C6-deficient rabbits.Immunology 38, 245–8.

    Google Scholar 

  • 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 xenografts: a review of progress.Immunol. Today 11, 450–6.

    Google Scholar 

  • Platt, J. L., Dalmasso, A. P., Vercellotti, G. M., Lindman, B. J., Turman, M. A. &Bach, F. H. (1990b) Endothelial cell proteoglycans in xenotransplantation.Transplant. Proc. 22, 1066.

    Google Scholar 

  • Platt, J. L., Lindman, B. J., Chen, H., Spitalnik, S. L. &Bach, F. H. (1990c) Endothelial cell antigens recognized by xenoreactive human natural antibodies.Transplantation 50, 817–22.

    Google Scholar 

  • Pratschke, E., Land, W., Schilling, A., Pielsticker, K. & Brendel, W. (1975) Furtherin-vitro studies on the mechanism of hyperacute xenogeneic rejection reaction (HXAR).Langenbecks. Arch. Chir. (suppl.) 129–32.

  • Reemtsma, K. (1989) Xenografts.Transplant. Proc. 21, 517–8.

    Google Scholar 

  • Sachs, D. H. &Bach, F. H. (1990) Immunology of xenograft rejection.Hum. Immunol. 28, 245–51.

    Google Scholar 

  • Schilling, A., Land, W., Pratschke, E., Pielsticker, K. &Brendel, W. (1976) Dominant role of complement in the hyperacute xenograft rejection reaction.Surg. Gynecol. Obstet. 142, 29–32.

    Google Scholar 

  • Settaf, A., Meriggi, F., Van de Stadt, J., Gane, P., Crougneau, S., Reynes, M., Rouger, P. &Houssin, D. (1987) Delayed rejection of liver xenografts compared to heart xenografts in the rat.Transplant. Proc. 19, 1155–7.

    Google Scholar 

  • Shons, A. R., Kromrey, C. &Najarian, J. S. (1973) Heterophile antibodies in man.Eur. Surg. Res. 5, 26–36.

    Google Scholar 

  • Van De Stadt, J., Vendeville, B., Weill, B., Crougneau, S., Michel, A., Filipponi, F., Icard, P., Renoux, M., Louvel, A. &Houssin, D. (1988) Discordant xenografts in the rat. Additional effect of plasma exchange and cyclosporine, cyclophosphamide, or splenectomy in delaying hyperacute rejection.Transplantation 45, 514–8.

    Google Scholar 

  • Van Den Bogaerde, J., Aspinall, R., Wang, M.-W, Cary, N., Lim, S., Wright, L. &White, D. (1991) Induction of long-term survival of hamster heart xenografts in rats.Transplantation 52, 15–20.

    Google Scholar 

  • Wang, M.-W., Heap, R. B., King, I., Taussig, M. J. &Whyte, A. (1988) Anti-idiotypic antibody used for the localization of parenterally administered monoclonal antiprogesterone antibody in mice.Scand. J. Immunol. 28, 267–76.

    Google Scholar 

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  1. S. M. L. Lim

    Present address: Department of Surgery, National University Hospital, Lower Kent Ridge Road, 0511, Singapore

Authors and Affiliations

  1. Department of Surgery, University of Cambridge Clinical School, Level 9, Addenbrooke's Hospital, Hills Road, CB2 2QQ, Cambridge, UK

    M. -W. Wang, P. S. Johnston, L. J. Wright, S. M. L. Lim & D. J. G. White

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  2. P. S. Johnston
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  3. L. J. Wright
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Wang, M.W., Johnston, P.S., Wright, L.J. et al. Immunofluorescent localization of pig complement component 3, regardless of the presence or absence of detectable immunoglobulins, in hyperacutely rejected heart xenografts. Histochem J 24, 102–109 (1992). https://doi.org/10.1007/BF01082446

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  • DOI: https://doi.org/10.1007/BF01082446

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