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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2761-2768. Prepublished online as a Blood First Edition Paper on July 12, 2005; DOI 10.1182/blood-2004-12-4623. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4623v1 106/8/2761    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Weijer, S. Articles by van der Poll, T. Search for Related Content PubMed PubMed Citation Articles by Weijer, S. Articles by van der Poll, T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY A thrombomodulin mutation that impairs activated protein C generation results in uncontrolled lung inflammation during murine tuberculosis Sebastiaan Weijer, Catharina W. Wieland, Sandrine Florquin, and Tom van der Poll From the Laboratory of Experimental Internal Medicine and Departments of Pathology and Infectious Diseases, Tropical Medicine, and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Thrombomodulin (TM) plays an essential role in the generation of activated protein C (APC), a mediator with both anticoagulant and anti-inflammatory properties, and is preferentially expressed in lungs. To investigate the role of TM in the coagulant and inflammatory response in the lung during tuberculosis, mice with a mutation in the TM gene (Thbd), which results in a minimal capacity for APC generation (TMpro/pro mice), were intranasally infected with live virulent Mycobacterium tuberculosis. Whereas pulmonary tuberculosis was not associated with activation of coagulation in either wild-type or TMpro/pro mice, 5 weeks after infection TMpro/pro mice displayed an uncontrolled inflammatory response in their lungs, as reflected by higher lung weights, a diminished ability to form well-shaped granulomas, elevated levels of proinflammatory cytokines, and concurrently reduced concentrations of anti-inflammatory cytokines. During a 36-week follow-up after infection with a lower dose of M tuberculosis, 35% of TMpro/pro mice died from week 28 onward versus none of the wild-type mice, and the surviving TMpro/pro mice displayed increased lung inflammation accompanied by higher mycobacterial loads in liver and spleen. These data suggest that a TM mutation that impairs APC generation results in uncontrolled lung inflammation during tuberculosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. T. Keller, K. F. van der Sluijs, M. D. de Kruif, V. E. A. Gerdes, J. C. M. Meijers, S. Florquin, T. van der Poll, E. C. M. van Gorp, D. P. M. Brandjes, H. R. Buller, et al. Effects on Coagulation and Fibrinolysis Induced by Influenza in Mice With a Reduced Capacity to Generate Activated Protein C and a Deficiency in Plasminogen Activator Inhibitor Type 1 Circ. Res., November 24, 2006; 99(11): 1261 - 1269. [Abstract] [Full Text] [PDF]

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