Staphylococcal infections impair the mesothelial fibrinolytic system:The role of cell death and cytokine release

Bacterial peritonitis is a serious complication of peritonea] dialysis patients and of patients after abdominal surgery. Especially episodes due to Staphylococcus aureus can harm the peritoneum severely, resulting in peritoneal fibrosis. Human peritoneal mesothelial cells play a critical role in maintaining the integrity of the peritoneum, as they release components of the fibrinolytic system and regulate the influx of immune cells by expressing chemokines and adhesion molecules. Using cultured human peritoneal mesothelial cells (HMCs) and blood mononuclear cells,we analyzed the effect of different staphylococcal strains on mesothelial fibrinolysis and on inflammatory reactions and show that only S. aureus strains with an invasive and hemolytic phenotype decrease the production of fibrinolytic system components, most likely via cell death induction. Furthermore, HMCs react to invading staphylococci by enhanced expression of chemokines and adhesion molecules. Mononuclear cells were activated by all staphylococcal strains tested, and their culture supernatants impaired mesothelial fibrinolysis. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, efficiently enhanced the mesothelial fibrinolytic capacity under these inflammatory conditions, but did not protect HMCs against S. aureus-induced cell death. We conclude that only selected S. aureus strains decrease the release of fibrinolytic system components and provoke a mesothelial inflammatory response. These factors most likely contribute to peritoneal fibrosis and might account for the severe clinical presentation of S. aureus peritonitis.