| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | The Journal of Heart and Lung Transplantation | ||||
| Publisher: | ELSEVIER SCIENCE INC | ||||
| Place of Publication: | NEW YORK | ||||
| Volume: | 31 | ||||
| Number of Issue or Book Chapter: | 12 | ||||
| Page Range: | pp. 1293-1300 | ||||
| Date: | 2012 | ||||
| Institutions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie | ||||
| Identification Number: |
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| Keywords: | RANDOMIZED CONTROLLED-TRIAL; RAT RENAL ISOGRAFTS; TRANSPLANT RECIPIENTS; REDUCES INFLAMMATION; DONOR PRETREATMENT; ACUTE REJECTION; ACTIVATION; MODEL; INDUCTION; THERAPY; donor brain death; inflammatory graft activation; immune cells; Thymoglobulin | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 63060 |
Web of ScienceAbstract
BACKGROUND: Donor brain death (BD) triggers inflammatory graft activation that leads to impaired graft quality and outcome. We used a mouse BD model to investigate graft inflammation in cardiac transplants from immune-competent and immune-deficient donor animals. Effects of donor T-cell depletion were tested in an additional group of cardiac transplant recipients. METHODS: We analyzed systemic ...
Abstract
BACKGROUND: Donor brain death (BD) triggers inflammatory graft activation that leads to impaired graft quality and outcome. We used a mouse BD model to investigate graft inflammation in cardiac transplants from immune-competent and immune-deficient donor animals. Effects of donor T-cell depletion were tested in an additional group of cardiac transplant recipients. METHODS: We analyzed systemic and graft-specific inflammatory activation after BD in donors and in syngeneic recipients of hearts retrieved from BD donors. To dissect the role of donor-specific immune cells in communicating BD-triggered inflammation, immune-deficient T-cell-, B-cell-, and natural killer cell-deficient Rag2/double knockout mice and naive C57BL6 treated with anti-thymocyte globulin (Thymoglobulin; Genzyme Transplant, Cambridge, MA) were observed. RESULTS: Donor BD boosted lymphocyte activation in donors and recipients of syngeneic BD grafts. Lymphocyte activation was mitigated in recipients of immune-deficient and Thymoglobulin-treated BD donor grafts. Likewise, systemic and intra-graft levels of inflammatory cytokines interleukin -1, interleukin-6, interferon-gamma, and tumor necrosis factor-a were significantly reduced in immune-deficient and anti-thymocyte globulin-treated recipients. Dense lymphocyte infiltrates were detected in the hearts from untreated BD donors; in contrast, the hearts from donors treated with Thymoglobulin demonstrated a preserved structure with minimal infiltrates comparable with naive controls. CONCLUSION: BD triggers inflammatory graft activation communicated through ultra-graft immune cells. Donor treatment with Thymoglobulin prevented inflammatory immune activation and improved graft quality to levels comparable to living donor organs. J Heart Lung Transplant 2012; 31: 1293-300 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved.
Metadata last modified: 19 Dec 2024 09:33
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