Sodium hyaluronate increases the fibrinolytic response of human peritoneal mesothelial cells exposed to tumor necrosis factor alpha.

HYPOTHESIS Sodium hyaluronate interferes with the fibrin degrading capacity of human peritoneal mesothelial cells exposed to tumor necrosis factor (TNF) alpha. DESIGN Controlled laboratory experiment. INTERVENTION Human peritoneal mesothelial cells were harvested from 5 patients undergoing laparotomy and cultured in vitro. Cells were treated with TNF-alpha, a cytokine typically involved in peritoneal inflammation, and sodium hyaluronate was added in a final concentration of 0.1%, 0.2%, or 0.4%. Controls received medium only. After 24 hours' incubation, tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and plasminogen activator inhibitor type 1 (PAI-1) were measured in the medium and cell lysates using enzyme-linked immunosorbent assay techniques. Specific gene transcripts in cells treated with 0.4% sodium hyaluronate and controls were determined using a quantitative reverse transcription polymerase chain reaction. MAIN OUTCOME MEASURES Concentrations of tPA, uPA, and PAI-1, and their specific gene transcripts. RESULTS Sodium hyaluronate significantly increased tPA concentration in cell lysates without affecting its gene expression as determined after 24 hours (P =.02). The uPA concentration was significantly decreased by sodium hyaluronate in the medium but not in cell lysates (P<.0001). The uPA messenger RNA expression was 1000-fold increased compared with control. Sodium hyaluronate significantly decreased PAI-1 concentration in the medium and reduced its gene expression 500-fold (P =.04), while PAI-1 concentration in cell lysates did not change. CONCLUSION Sodium hyaluronate affected the fibrinolytic response of TNF-alpha-stimulated human peritoneal mesothelial cells, most notably by decreasing PAI-1 transcription and release. This observation indicates that sodium hyaluronate counteracts the fibrinolytic decline induced by TNF-alpha and suggests a biological mechanism of action for sodium hyaluronate intra-abdominally.