Title: The lectin-like domain of thrombomodulin protects against ischaemia-reperfusion lung injury
Authors: Geudens, Nele ×
Van de Wouwer, Marlies
Vanaudenaerde, Bart
Vos, Robin
Van De Wauwer, Caroline
Verleden, Geert
Verbeken, Eric
Lerut, Antoon
Van Raemdonck, Dirk
Conway, Edward #
Issue Date: Oct-2008
Publisher: Published jointly by the Society and Munksgaard
Series Title: European Respiratory Journal vol:32 issue:4 pages:862-870
Abstract: Ischaemia-reperfusion injury of the lung is a major cause of morbidity and mortality, particularly following lung transplantation, the mainstay treatment for patients with end-stage pulmonary disease. Effective measures to prevent this complication are lacking. Thrombomodulin (TM) is an endothelial cell receptor and cofactor for thrombin-mediated generation of the anticoagulant and anti-inflammatory activated protein C (APC). The N-terminal lectin-like domain (LLD) of TM has no direct effects on coagulation, but has distinct anti-inflammatory properties, interfering with leukocyte adhesion, complement activation and cytokine generation, all of which are hallmarks of ischaemia-reperfusion injury. Using a murine model of lung ischaemia-reperfusion injury (90 min ischaemia, 4 h reperfusion), the present study shows that mice lacking the LLD of TM respond with increased extravasation of neutrophils and macrophages into the lung parenchyma and bronchoalveolar fluid (BALF), with augmented BALF levels of cytokines interleukin (IL)-1beta and granulocyte-monocytic colony-stimulating factor (GM-CSF). Pre-treatment of wild-type mice with recombinant LLD, as compared with controls, significantly suppresses protein leakage and accumulation of leukocytes in the BALF. These novel findings support further evaluation of recombinant lectin-like domain of thrombomodulin to protect the lung against tissue-damaging pro-inflammatory responses following ischaemia-reperfusion.
ISSN: 0903-1936
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pneumology
Translational Cell & Tissue Research
Thoracic Surgery
Vesalius Research Centre (-)
Molecular and Vascular Biology
Laboratory for Pharmaceutical Biology (-)
× corresponding author
# (joint) last author

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