Palomo, Marta and Diaz-Ricart, Maribel and Carbo, Carla and Rovira, Montserrat and Fernandez-Aviles, Francesc and Escoar, Gines and Eissner, Guenther and Holler, Ernst and Carreras, Enric (2009) The Release of Soluble Factors Contributing to Endothelial Activation and Damage after Hematopoietic Stem Cell Transplantation Is Not Limited to the Allogeneic Setting and Involves Several Pathogenic Mechanisms. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 15 (5). pp. 537-546. ISSN 1083-8791, 1523-6536
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This study evaluated the relative impact of the intensity of the conditioning regimen and the alloreactivity in the endothelial dysfunction occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It involved a comparative analysis of the effect of incubating human umbilical vein endothelial cells (ECs) with serum samples from patients receiving autologous HSCT (auto-HSCT) or unrelated donor allo-HSCT In both groups, blood samples were collected through a central line before conditioning (Pre), before transplantation (day 0), and at days 7, 14, and 21 after transplantation. Changes in the expression of EC receptors and adhesion proteins, adhesion of leukocytes and platelets under flow, and signaling pathways were analyzed. Endothelial activation and damage were observed in both groups, but with differing patterns. All markers of endothelial dysfunction demonstrated a progressive increase from day Pre to day 14 in the auto-HSCT group and exhibited 2 peaks of maximal expression (at days 0 and 21) in the allo-HSCT group. Both treatments induced a proinflammatory state (ie, expression of adhesion receptors, leukocyte adhesion, and p38 MAPK activation) and cell proliferation (ie, morphology and activation of ErK42/44). Prothrombotic changes (ie, von Willebrand factor expression and platelet adhesion) predominated after allo-HSCT, and a proapoptotic tendency (ie, activation of SAPK/JNK) was seen only in this group. These findings indicate that endothelial activation and damage after HSCT also occur in the autologous setting and affect macrovascular ECs. After the initial damage induced by the conditioning regimen, other factors, such as granulocyte colony-stimulating factor (G-CSF) toxicity, engraftment, and alloreactivity, may contribute to the endothelial damage seen during HSCT Further studies are needed to explore the association between this endothelial damage and the vascular complications associated with HSCT.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ADHESION MOLECULES; FLOW CONDITIONS; IN-VITRO; VASCULAR ENDOTHELIUM; EXTRACELLULAR-MATRIX; BACTERIAL-ENDOTOXIN; PLATELET-ADHESION; COMPLICATIONS; Endothelial activation; Hematopoietic stem cell transplantation; Early complications |
| 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: | 16 Sep 2020 05:11 |
| Last Modified: | 16 Sep 2020 05:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29004 |
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