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Thromb Haemost 2014; 111(02): 345-353
DOI: 10.1160/TH13-08-0719
Animal Models
Schattauer GmbH

The thrombomodulin lectin-like domain does not change host responses to tuberculosis

Liesbeth M. Kager
1   Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
2   Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
,
Alex F. de Vos
1   Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
2   Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
,
Joris J. T. H. Roelofs
3   Department of Pathology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
,
Chris M. van der Loos
3   Department of Pathology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
,
Onno J. de Boer
3   Department of Pathology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
,
Cornelis van’t Veer
1   Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
2   Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
,
Edward M. Conway
5   Centre for Blood Research, Life Sciences Institute, Division of Hematology-Oncology, Faculty of Medicine, University of British Columbia, Vancouver, Canada
,
Tom van der Poll
1   Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
2   Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
4   Division of Infectious Diseases, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
› Author Affiliations Financial support: This work was sponsored by research grants of ZonMW (to L. M. K., grant number 92003504), the Stichting BeGeTu (to L. M. K.), the Mr. Willem Bakhuys Roozeboom Stichting (to L. M. K.). E.M.C. holds a CSL-Behring Chair and a Canada Research Chair in Endothelial Cell Biology and is supported by the Canadian Institutes for Health Research and the Natural Sciences and Engineering Council of Canada.
Further Information

Publication History

Received: 30 August 2013

Accepted: 17 September 2013

Publication Date:
27 November 2017 (online)

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Summary

Tuberculosis (TB), caused by Mycobacterium (M.) tuberculosis, is a devastating infectious disease causing many deaths world-wide. Thrombomodulin (TM) is a multidomain glycoprotein expressed on all vascular endothelial cells. We here studied the role of the lectin-like domain of TM, responsible for a variety of anti-inflammatory properties of TM, during TB. We compared the extent of TM-expression in human lung tissue of TB and control patients. The, the role of the lectin-like domain of TM was investigated by comparing mice lacking this domain (TMLeD/LeD mice) with wild-type (WT) mice during experimental lung TB induced by infection with M. tuberculosis via the airways. Lungs were harvested for analyses at two, six and 29 weeks after infection. Lung TM-expression was downregulated in TB patients, which was not related to changes in the amount of endothelium in infected lungs. TMLeD/LeD mice showed unaltered mycobacterial loads in lungs, liver and spleen during experimental TB. Additionally, lung histopathology and cytokine concentrations were largely similar in TMLeD/LeD and WT mice, while total leukocyte counts were increased in lungs of TMLeD/LeD mice after 29 weeks of infection. Mortality did not occur in either group. The lectin-like domain of TM does not play an important role in the host response to M. tuberculosis infection in mice.

Keywords

Tuberculosis - inflammation - thrombomodulin - lung - infection
 

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