protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia a controlled laboratory studyprotease-activated receptor-1损害宿主防御在小鼠肺炎球菌肺炎受控的实验室研究.pdfVIP

Schouten et al. Critical Care 2012, 16:R238 /content/16/6/R238 RESEARCH Open Access Protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia: a controlled laboratory study 1,2* 1,2 3 4 1,2,5 Marcel Schouten , Cornelis van’t Veer , Joris JTH Roelofs , Marcel Levi and Tom van der Poll 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. Introduction involved in the coagulation system. Intriguingly, activa- Streptococcus (S.) pneumoniae or the pneumococcus is tion of PAR-1 can result in opposite cellular effects the number one causative pathogen in community-