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Published in: Critical Care 6/2012

Open Access 01-12-2012 | Research

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

Authors: Marcel Schouten, Cornelis van't Veer, Joris JTH Roelofs, Marcel Levi, Tom van der Poll

Published in: Critical Care | Issue 6/2012

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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.
Appendix
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Metadata
Title
Protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia: a controlled laboratory study
Authors
Marcel Schouten
Cornelis van't Veer
Joris JTH Roelofs
Marcel Levi
Tom van der Poll
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Critical Care / Issue 6/2012
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc11910

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