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

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 effe...

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Veröffentlicht in:	Critical care (London, England) Jg. 16; H. 6; S. R238
Hauptverfasser:	Schouten, Marcel, van't Veer, Cornelis, Roelofs, Joris JTH, Levi, Marcel, van der Poll, Tom
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London BioMed Central 27.12.2012 BioMed Central Ltd
Schlagworte:	Animals Blood Chemokines - blood Critical Care Medicine Cytokines - blood Emergency Medicine Histochemistry Immunity - physiology Infection Inflammation Inflammation - physiopathology Intensive Leukocytes (neutrophilic) Liver Lung Medicine Medicine & Public Health Mice Mice, Inbred C57BL Mice, Knockout Neutrophil Infiltration - physiology Pathogens Pneumonia Pneumonia, Pneumococcal Pneumonia, Pneumococcal - immunology Pneumonia, Pneumococcal - mortality Pneumonia, Pneumococcal - physiopathology Proteases Proteinase Proteinase-activated receptor 1 Receptor, PAR-1 - physiology Spleen Streptococcus pneumoniae Lower Bacterial Load Barrier Protective Effect Antibacterial Defense Proinflammatory Signaling Pathway Pneumococcal Pneumonia
ISSN:	1364-8535, 1466-609X, 1364-8535, 1466-609X
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	1364-8535 1466-609X 1364-8535 1466-609X
DOI:	10.1186/cc11910