PT  - JOURNAL ARTICLE
AU  - Ricardo José
AU  - Andrew Williams
AU  - Michal Sulikowski
AU  - Natalia Smoktunowicz
AU  - Paul Mercer
AU  - Jeremy Brown
AU  - Rachel Chambers
TI  - LSC 2014 abstract - Proteinase activated receptor-1 (PAR1) plays a key role in the early inflammatory response to streptococcus pneumoniae pulmonary infection
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - 478
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/478.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/478.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Introduction: S. pneumoniae is the most common cause of community acquired pneumonia and may result in an exaggerated inflammatory response associated with lung injury. PAR1 has been implicated in coagulation-inflammation cross-talk but its role in pneumococcal-induced pulmonary inflammation is poorly understood.Methods: BALB/c mice were challenged intranasally with S. pneumoniae (D39) or PBS followed by an intraperitoneal injection of a highly selective PAR1 antagonist SCH530348 (or vehicle) every 12 h. Mice were culled at 4, 24 and 48 h. In separate experiments paraffin embeded lung slices were immunostained for PAR1, Ly6G and S. pneumoniae.Results: S. pneumoniae infection resulted in increased bronchoalveolar lavage fluid (BALF) neutrophil counts and albumin levels, as well as increased levels of whole lung TNF-α, IL-1β, IL-6, IFNγ, KC, CCL2 and CCL7. On immunohistochemical analysis, areas of Ly6G staining correlated with areas of S. pneumoniae staining. PAR1 antagonism significantly reduced BALF neutrophil counts at 4 and 24 h, and attenuated the increase in IL-1β, CCL2 and CCL7 levels at 4 h following S. pneumoniae challenge. Bacterial counts in BALF, lung homogenates and blood were not affected by PAR1 antagonism at any of the time points examined. Additionally, PAR1 antagonism attenuated albumin levels from recovered BALF at 24 h.Conclusion: PAR1 antagonism attenuates S. pneumoniae-induced early neutrophilic inflammation and alveolar barrier disruption without compromising host defence.