Eissner, Guenther and Iacobelli, M. and Blueml, S. and Burger, V. and Haffner, S. and Andreesen, Reinhard and Holler, Ernst (2005) Oligotide, a defibrotide derivative, protects human microvascular endothelial cells against fludarabine-induced activation, damage and allogenicity. BONE MARROW TRANSPLANTATION, 35 (9). pp. 915-920. ISSN 0268-3369,
Full text not available from this repository. (Request a copy)Abstract
Fludarabine is a nonmyeloablative immunosuppressant increasingly used as a component of alternative reduced-intensity conditioning regimens prior to allogeneic stem cell transplantation (SCT). However, we have previously shown that 2-fluoroadenine 9-beta-D-arabinofuranoside (F-Ara) as the active metabolized form of fludarabine induces damage, activation and allogenicity in human microvascular endothelial cells (HMEC). We had also identified the pharmaceutic compound Defibrotide (DF), originally used in the treatment of veno-occlusive disease and thrombotic microangiopathy, as being protective against F-Ara-induced dysfunction of HMEC, importantly, without affecting the antileukemic effect of F-Ara. In the present report, we show that a recently developed derivative of DF, Oligotide, similarly downregulates F-Ara-induced activation and damage of HMEC as well as their antigenicity for allogeneic CD8 + T cells. In addition, Oligotide could also block F-Ara-mediated transendothelial migration of peripheral blood cells across the HMEC barrier. Taken together, these observations argue for a potential clinical use of both DF and Oligotide in pre transplant conditioning.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RADIATION-INDUCED ACTIVATION; SEVERE VENOOCCLUSIVE DISEASE; HIGH-RISK POPULATION; VERSUS-HOST-DISEASE; IN-VITRO; TRANSENDOTHELIAL MIGRATION; BACTERIAL-ENDOTOXIN; SIGNIFICANT TOXICITY; COMPASSIONATE-USE; RAT-KIDNEY; endothelial cells; Oligotide; fludarabine |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 May 2021 06:50 |
| Last Modified: | 14 May 2021 06:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36159 |
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