Title: Transgenic tissue-type plasminogen activator expression improves host defense during Klebsiella pneumonia
Authors: Renckens, R
Roelofs, J J T H
Stegenga, M E
Florquin, S
Levi, M
Carmeliet, Peter
Van't Veer, C
van der Poll, T # ×
Issue Date: Apr-2008
Series Title: Journal of Thrombosis and Haemostasis vol:6 issue:4 pages:660-668
Abstract: BACKGROUND: Severe pneumonia is associated with a local inhibition of fibrinolysis in the lung as reflected by strongly reduced pulmonary plasminogen activator activity.Objectives: To study the effect of elevation of local plasminogen activator activity during pneumonia caused by the common respiratory pathogen Klebsiella pneumoniae. METHODS: Female C57Bl/6 mice were inoculated intranasally with a replication-defective adenoviral vector expressing human tissue-type plasminogen activator or a control vector 24 h before intranasal infection with K. pneumoniae. RESULTS: Mice infected with Klebsiella via the airways developed overt pneumonia, which was accompanied by a downregulation of pulmonary tissue-type plasminogen activator levels at protein and mRNA levels. Pulmonary overexpression of human tissue-type plasminogen activator resulted in increased fibrinolytic activity in the lungs during pneumonia, as indicated by higher D-dimer levels and reduced fibrin deposition. Interestingly, overexpression of tissue-type plasminogen activator markedly improved host defense against pneumonia: mice treated with the tissue-type plasminogen activator vector displayed less bacterial growth and dissemination, attenuated distant organ injury and a reduced mortality. CONCLUSIONS: These data demonstrate that local elevation of plasminogen activator activity in the lungs improves host defense against severe gram-negative pneumonia and sepsis.
ISSN: 1538-7933
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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