Binding of ATGs to endothelial cells in vivo
- BACKGROUND: Polyclonal anti-thymocyte globulins (ATGs) are immunosuppressive drugs widely used in induction of immunosuppression and treatment of acute rejection after solid organ transplantation. We have previously demonstrated that ATGs bind to endothelial cells in vitro, and are able to modulate ECs. The aim of this study was to investigate the binding of ATGs to endothelial cells under in vivo conditions. MATERIAL AND METHODS: Muscle biopsies from extremities of cynomolgus monkeys were obtained after ischemia/reperfusion at 4°C. ATGs (Thymoglobulin, Sanofi-Aventis, France; 1 mg/kg) were added to the blood 30 min prior to the reperfusion. Biopsies (n=10) of patients undergoing heart transplantation and preoperatively treated with ATGs (Thymoglobulin, Sanofi-Aventis, France; 1.5 mg/kg) as induction therapy were also analyzed 6 hours and 7 days after induction. Binding of ATGs to ECs was analyzed with an anti-rabbit IgG antibody by means of immunohistochemistry. RESULTS: Binding of ATGs to endothelial cells could be demonstrated in vivo in our animal experiments 4 hours after reperfusion, as well as in the clinical biopsies 6 hours after induction of immunosuppression in heart transplant patients, showing a preferred localization in post-capillary veins. No expression of ATGs on the endothelial surface could be observed after 7 days, suggesting that ATGs may be washed out from the endothelial surface in a time-dependent manner. CONCLUSIONS: Our results show that ATGs are able to bind to endothelial cells in an experimental model and in clinical practice, supporting preconditioning strategies with ATGs in solid organ transplantation.
Author: | Andrés Beiras FernándezGND, Astrid Hernandez-Sierra, Uwe Schulz, Manfred Richter, Eckart Thein, Anton Moritz, Isabella Werner |
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URN: | urn:nbn:de:hebis:30:3-430101 |
DOI: | https://doi.org/10.12659/AOT.896158 |
ISSN: | 1425-9524 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/27184761 |
Parent Title (English): | Annals of transplantation |
Publisher: | Polish Transplantation Society with the co-operation of the Czech Transplantation Society and the Hungarian Transplantation Society |
Place of publication: | Warsaw |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2017/03/16 |
Year of first Publication: | 2016 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2017/03/16 |
Tag: | Heart transplantation; Immunosuppressive agents; endothelial cells |
Volume: | 21 |
Page Number: | 6 |
First Page: | 311 |
Last Page: | 316 |
Note: | This paper has been published under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. |
HeBIS-PPN: | 424805235 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |