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Sodium Hyaluronate Increases the Fibrinolytic Response of Human Peritoneal Mesothelial Cells Exposed to Tumor Necrosis Factor 
Michel M. P. J. Reijnen, MD;
Harry van Goor, MD, PhD;
Peter Falk, BSc;
Maria Hedgren, BSc;
Lena Holmdahl, MD, PhD
Arch Surg. 2001;136:291-296.
Hypothesis Sodium hyaluronate interferes with the fibrin degrading capacity of human peritoneal mesothelial cells exposed to tumor necrosis factor (TNF)  .
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-, 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-–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- and suggests a biological mechanism of action for sodium hyaluronate intra-abdominally.
From the Department of Surgery, University Hospital Nijmegen, Nijmegen, the Netherlands (Drs Reijnen and van Goor) and Sahlgrenska University Hospital/Östra, Göteborg University, Göteborg, Sweden (Mr Falk, Ms Hedgren, and Dr Holmdahl).
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