Influence of monocyte-like cells on the fibrinolytic activity of peritoneal mesothelial cells and the effect of sodium hyaluronate

Objective: To determine whether the presence of cells of the monocyte-macrophage system affects the fibrinolytic response of peritoneal mesothelial cells to lipopolysaccharide (LPS) in the presence and absence of sodium hyaluronate. Design: Controlled laboratory experiment. Setting: Cell cultures in an academic laboratory research environment. Patient(s): Human peritoneal mesothelial cells were harvested from patients undergoing a laparotomy for noninfectious reasons and were cultured in vitro. Co-cultures were formed by adding U-937 human monocyte-like cells to a monolayer of mesothelial cells. Intervention(s): After 24 hours, cultures were treated with 10 ng/mL of LPS, and sodium hyaluronate was added in a final concentration of 0.2%. Controls received medium without sodium hyaluronate. Main Outcome Measure(s): After 24 hours' incubation, tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), and plasminogen activator inhibitor-1 (PAI-1) levels were determined in medium and cell lysates by using ELISA techniques. Result(s): In medium of co-cultures, tPA and PAI-1 concentrations were statistically significantly increased compared with the case of monocultures, whereas uPA concentration was statistically significantly decreased. In cell lysates of co-cultures, PAI-1 concentration was statistically significantly increased compared with the case of monocultures, whereas tPA and uPA were unaffected. Treatment with sodium hyaluronate statistically significantly decreased PAI-1 and uPA concentrations in medium of monocultures but decreased uPA concentration only in medium of co-cultures, compared with the case of controls. Conclusion(s): Cells of the monocyte-macrophage system modulate the fibrinolytic capacity of LPS treated human peritoneal mesothelial cells and interfere in the hyaluronan-associated changes in mesothelial fibrinolytic capacity.