Endogenous tissue-type plasminogen activator impairs host defense during severe experimental Gram-negative sepsis (melioidosis)*

Critical Care Medicine
Liesbeth M KagerTom van der Poll

Abstract

Melioidosis is a frequent cause of severe sepsis in Southeast Asia caused by the gram-negative bacterium Burkholderia pseudomallei. Patients with melioidosis have elevated circulating levels of tissue-type plasminogen activator, an important regulator of fibrinolysis. In this study, we aimed to investigate the role of tissue-type plasminogen activator during melioidosis. Animal study. University research laboratory. Wild-type and tissue-type plasminogen activator-deficient C57BL/6 mice. Mice were intranasally infected with viable Burkholderia pseudomallei and killed after 24, 48, or 72 hrs for harvesting of lungs, liver, and blood. Additionally, survival studies were performed. Experimentally induced melioidosis was associated with elevated levels of tissue-type plasminogen activator in lungs of infected wild-type mice. During infection with Burkholderia pseudomallei, tissue-type plasminogen activator-deficient mice were protected when compared to wild-type mice as demonstrated by a strongly decreased mortality (62% vs. 100% amongst wild-type mice, p < .0001), together with decreased pulmonary bacterial loads, less severe histopathological scores, and decreased fibrinolysis. These results were accompanied with an early increase...Continue Reading

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Citations

Sep 3, 2013·American Journal of Respiratory and Critical Care Medicine·Liesbeth M KagerTom van der Poll
Oct 21, 2015·Critical Reviews in Microbiology·Marijke PeetermansPeter Verhamme
Nov 18, 2015·Thrombosis Research·Lionel LattenistJoris J T H Roelofs
Apr 4, 2014·Thrombosis and Haemostasis·Tom van der Poll, Heiko Herwald
Dec 12, 2012·Journal of Thrombosis and Haemostasis : JTH·L M KagerT van der Poll
Apr 4, 2019·Interventional Neuroradiology : Journal of Peritherapeutic Neuroradiology, Surgical Procedures and Related Neurosciences·Zenith KhashimDavid F Kallmes
Jun 20, 2012·Critical Care Medicine·Perenlei Enkhbaatar, Daniel L Traber
Sep 26, 2013·Critical Care Medicine·Perenlei Enkhbaatar
Jan 9, 2014·Critical Care Medicine·Liesbeth M KagerTom van der Poll
Jun 26, 2014·Expert Review of Anti-infective Therapy·Liesbeth Martine KagerWillem Joost Wiersinga

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