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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1593-1601. Prepublished online as a Blood First Edition Paper on October 10, 2006; DOI 10.1182/blood-2006-05-025197. This Article Full Text (PDF) All Versions of this Article: blood-2006-05-025197v1 109/4/1593    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Renckens, R. Articles by van der Poll, T. Search for Related Content PubMed PubMed Citation Articles by Renckens, R. Articles by van der Poll, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 23, 2006 Accepted September 25, 2006 Plasminogen activator inhibitor type 1 is protective during severe Gram-negative pneumonia Rosemarijn Renckens*, Joris J.T.H, Roelofs, Peter I. Bonta, Sandrine Florquin, Carlie J. M. de Vries, Marcel M. Levi, Peter Carmeliet, Cornelis van 't Veer, and Tom van der Poll Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Netherlands Academic Medical Center, University of Amsterdam, Netherlands University of Leuven, Belgium * Corresponding author; email: r.renckens{at}amc.uva.nl. Plasminogen activator inhibitor type-1 (PAI-1) levels are consistently elevated in patients with severe pneumonia and sepsis and highly predictive for an unfavorable outcome. In addition, pneumonia is associated with strongly elevated PAI-1 levels in the pulmonary compartment. However, whether PAI-1 causally affects antibacterial host defense in vivo remains unknown. We report here that pneumonia caused by the common respiratory pathogen Klebsiella pneumoniae is associated with local production of PAI-1 in the lungs of wild-type mice. PAI-1 deficiency impaired host defense as reflected by enhanced lethality and increased bacterial growth and dissemination in mice with a targeted deletion of the PAI-1 gene. Conversely, transgenic overexpression of PAI-1 in the lung using a replication defective adenoviral vector markedly improved host defense against Klebsiella pneumonia and sepsis. PAI-1 deficiency reduced accumulation of neutrophils in the lungs during pneumonia, whereas PAI-1 overexpression in healthy lungs resulted in neutrophil influx, suggesting that PAI-1 protects the host against Klebsiella pneumonia by promoting neutrophil recruitment to the pulmonary compartment. These data demonstrate for the first time that PAI-1 is essential for host defense against severe Gram-negative pneumonia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. B. Allen, M. E. Cloutier, Y. C. Larrabee, K. Tetenev, S. T. Smiley, and J. H. T. Bates Neither fibrin nor plasminogen activator inhibitor-1 deficiency protects lung function in a mouse model of acute lung injury Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L277 - L285. [Abstract] [Full Text] [PDF] Y.-J. Park, G. Liu, E. F. Lorne, X. Zhao, J. Wang, Y. Tsuruta, J. Zmijewski, and E. Abraham PAI-1 inhibits neutrophil efferocytosis PNAS, August 19, 2008; 105(33): 11784 - 11789. [Abstract] [Full Text] [PDF] M. Schouten, W. J. Wiersinga, M. Levi, and T. van der Poll Inflammation, endothelium, and coagulation in sepsis J. Leukoc. Biol., March 1, 2008; 83(3): 536 - 545. [Abstract] [Full Text] [PDF]

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