Summary
Bacterial peritonitis is a serious complication of peritoneal 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.
Keywords
Bacterial peritonitis - peritoneal fibrosis - mesothelial fibrinolytic system - statins
