Natural anti-galactose α1,3 galactose antibodies delay, but do not prevent the acceptance of extracellular matrix xenografts
| Autor: | Roberta Raeder, Bhaskar V. S. Kallakury, Dennis W. Metzger, Stephen F. Badylak, Christine E. Sheehan |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Swine
Xenotransplantation medicine.medical_treatment Transplantation Heterologous Immunology Alpha (ethology) Disaccharides Antibodies Epitope Mice chemistry.chemical_compound Intestine Small medicine Animals Immunology and Allergy Complement Activation Galactosyltransferase Transplantation biology Molecular biology Extracellular Matrix Complement system Mice Inbred C57BL Immunoglobulin M chemistry Mice Inbred DBA Galactose biology.protein Rabbits Antibody |
| Zdroj: | Transplant Immunology. 10:15-24 |
| ISSN: | 0966-3274 |
| Popis: | Naturally occurring antibodies to the galactose alpha1,3 galactose (alpha gal) epitope expressed on xenogeneic grafts are a major barrier to organ transplantation in humans. Porcine small intestinal submucosa (SIS) expresses the alpha gal epitope and is currently being used as a bioscaffold for tissue remodeling. To examine in detail the potential role of the alpha gal epitope in immune recognition of this acellular, avascular biomaterial, we have used mice which have a genetic disruption in the alpha1,3 galactosyltransferase gene (alpha gal(-/-)mice) and thus express natural anti-alpha gal antibodies in a manner similar to humans. It was found that alpha gal(-/-)mice produced IgM anti-alpha gal antibodies in addition to IgG1 SIS-specific antibodies, which did not bind to the alpha gal epitope. Histological examination of implant sites demonstrated an early inflammatory response that consisted predominantly of neutrophils in both alpha gal(+/+) and alpha gal(-/-)mice. However, while alpha gal(+/+)mice completely remodeled SIS implants by day 25, alpha gal(-/-)mice still exhibited some visible SIS together with inflammatory cellular infiltrates at this time point. Nevertheless, by day 35, the implant site in alpha gal(-/-)mice appeared to be entirely remodeled although a few acute inflammatory cells were still present. Immunization of alpha gal(-/-)mice with sheep erythrocytes to enhance anti-alpha gal antibody levels led to a more robust early inflammatory response following implantation but did not change the ultimate fate of the graft. We conclude that, in contrast to xenotransplantation of whole organs, naturally-occurring anti-alpha gal antibodies do not influence the ability of xenogeneic extracellular matrices to serve as bioscaffolds for tissue remodeling. |
| Databáze: | OpenAIRE |
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