title: Protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia: a controlled laboratory study.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  PAR-1 impairs host defense during murine pneumococcal pneumonia.
authors.forename: Marcel
authors.initials: M
authors.lastname: Schouten
authors.forename: Cornelis
authors.initials: C
authors.lastname: van't Veer
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D007109:Immunity / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000502:physiology; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D044463:Receptor, PAR-1 / Q000502:physiology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D044463:Receptor, PAR-1