title: Binding of ATGs to Endothelial Cells In Vivo.
abstract: 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.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, JW Goethe University, Frankfurt, Germany.
authors.forename: Andres
authors.initials: A
authors.lastname: Beiras-Fernandez
authors.affiliation: Department of Nephrology, Autonomous University of Bucaramanga (UNAB), Bucaramanga, Colombia.
authors.forename: Astrid
authors.initials: A
authors.lastname: Hernandez-Sierra
authors.affiliation: Department of Cardiac Surgery, Das Herz- und Diabeteszentrum (HDZ), Bad Oynhausen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schulz
authors.affiliation: Department of Cardiac Surgery, Kerkhoff-Klinik, Bad Nauheim, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Richter
authors.affiliation: Institute for Surgical Research, Ludwig-Maximilian-University, Munich, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Thein
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, JW Goethe University, Frankfurt, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Moritz
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, JW Goethe University, Frankfurt, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Werner
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000627:therapeutic use; D042783:Endothelial Cells / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D016027:Heart Transplantation / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008252:Macaca fascicularis; D009130:Muscle, Smooth / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents