Antifibrinolytische Eigenschaften humaner Mesothelzellen in vitro in Interaktion mit isolierten neutrophilen Granulozyten

One of the most important complications of abdominal surgery is the formation of postoperative adhesions. A major factor for adhesion formation is an inbalance of pro- and antifibrinolytic intraabdominal processes. Deposition of a fibrin-rich exsudate leads fibroblasts to organisate the exsudate. A permanent adhesion with the fatal complication of inducing an ileus develops. One of the key players in regulation the pro- and antifibrinolytic process are mesothelial cells, the biggest cell population intraabdominal. They produce the fibrinolytic enzyme t-PA (tissue plasminogen-activator) and its inhibitor PAI-1 (plasminogen-activator-inhibitor-1). Our investigations of cultured human mesothelial cells show an increase of PAI-1 and a decrease of t-PA concentration under inflammatoric stimulation. We used TNF-alpha (tumor-necrosis-factor-alpha), TGF-beta (transforming-growth-factor-beta) und IL-1beta (interleucin-1beta) for stimulation. Our fibrin-clot model allowed an investigation of the time-dependant effects. Moreover we investigated the influence of activated granulocytes on the fibrinolytic potency of the mesiothelial cells. A stimulation of the HOMC with supernatants of granulocytes leaded to a decrease of PAI-1 secretion and therefore to an apparent support of the lytic process. It was not clear if this effect was based on the regulatoric function of the granulocytes or on the cell destruction of the mesothelial cells, which was caused by superoxyd ions, hydrogenperoxyd and hydroxid radicals, produced by the granulocytes