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

Hypothesis: Sodium hyaluronate interferes with the fibrin degrading capacity of human peritoneal mesothelial cells exposed to tumor necrosis factor (TNF) α.

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-α, 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-α-stimulated human peritoneal mesothelial cells, most notably by decreasing PA1-1 transcription and release. This observation indicates that sodium hyaluronate counteracts the fibrinolytic decline induced by TNF-α and suggests a biological mechanism of action for sodium hyaluronate intra-abdominally.