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Open Access Research

Protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia: a controlled laboratory study

Marcel Schouten12*, Cornelis van't Veer12, Joris JTH Roelofs3, Marcel Levi4 and Tom van der Poll125

Author Affiliations

1 Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

2 Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

3 Department of Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

4 Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

5 Division of Infectious Diseases; Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

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Critical Care 2012, 16:R238  doi:10.1186/cc11910


See related Commentary by Asehnoune et al., http://ccforum.com/content/17/1/119

Published: 27 December 2012

Abstract

Introduction

Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. Protease-activated receptor-1 (PAR-1) is expressed by multiple cell types present in the lungs and can be activated by various proteases generated during acute inflammation. The cellular effect of PAR-1 activation partially depends on the specific protease involved. We here determined the role of PAR-1 in the host response during murine pneumococcal pneumonia.

Methods

Wild-type (WT) and PAR-1 knockout (KO) mice were infected intranasally with viable S. pneumoniae and observed in a survival study or euthanized at 6, 24 or 48 hours of infection.

Results

PAR-1 KO mice had a better survival early after infection compared to WT mice. Moreover, PAR-1 KO mice had lower bacterial loads in lungs and blood at 24 hours and in spleen and liver at 48 hours after infection. This favorable response was accompanied by lower lung histopathology scores and less neutrophil influx in PAR-1 KO mice.

Conclusion

PAR-1 impairs host defense during murine pneumococcal pneumonia.