Role of PAR2 in murine pulmonary pseudomonal infection

Proteinases can influence lung inflammation by various mechanisms, including via cleavage and activation of protease-activated receptors (PAR) such as PAR2. In addition, proteinases such as neutrophil and/or Pseudomonas-derived elastase can disarm PAR2 resulting in loss of PAR2 signaling. Currently, the role of PAR2 in host defense against bacterial infection is not known. Using a murine model of acute Pseudomonas aeruginosa pneumonia, we examined differences in the pulmonary inflammatory response between wild-type and PAR2−/− mice. Compared with wild-type mice, PAR2−/− mice displayed more severe lung inflammation and injury in response to P. aeruginosa infection as indicated by higher bronchoalveolar lavage fluid neutrophil numbers, protein concentration, and TNF-α levels. By contrast, IFN-γ levels were markedly reduced in PAR2−/− compared with wild-type mice. Importantly, clearance of P. aeruginosa was diminished in PAR2−/− mice. In vitro testing revealed that PAR2−/− neutrophils killed significantly le...