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Thromb Haemost 1990; 64(03): 420-425
DOI: 10.1055/s-0038-1647330
Original Article
Schattauer GmbH Stuttgart

Heparin Stimulates Fibrinolysis in Mesothelial Cells by Selective lnduction of Tissue-Plasminogen Activator but not Plasminogen Activator Inhibitor-l Synthesis

Jürgen Grulich-Henn
The Max-Planck-Gesellschaft, Clinical Research Unit for Blood Coagulation and Thrombosis, GieBen, fuderal Republic of Germany
,
Klaus T Preissner
The Max-Planck-Gesellschaft, Clinical Research Unit for Blood Coagulation and Thrombosis, GieBen, fuderal Republic of Germany
,
Gert Müller-Berghaus
The Max-Planck-Gesellschaft, Clinical Research Unit for Blood Coagulation and Thrombosis, GieBen, fuderal Republic of Germany
› Author Affiliations
Further Information

Publication History

Received: 19 January 1990

Accepted after revision08 June 1990

Publication Date:
25 July 2018 (online)

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Summary

The regulation of tissue-plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-l) synthesis was studied in cultured human mesothelial cells derived from omentum (HOMC). Heparin (100 U/ml) as well as pentosan polysulfate (300 pg/mt) stimulated tPA synthesis by HOMC 2.9-4.5-fold. Heparin-induced tPA production was dose- and time-dependent and was inhibited by cycloheximide. tPA production by HOMC was also stimulated by phorbol 12-myristrate l3-acetat (2.6-fold), fibrin clots (1.9-fold), or batroxobin (1.9-fold).Heparin and pentosan polysulfate did not stimulate PAI-1 production by HOMC, while phorbol l2-myristrate 13-acetat (100 nM) increased the concentration of PAI-1 in the conditioned medium by 2.6-fold over 24 h. The interaction of heparin with HOMC was studied by direct binding experiments. Dose-dependent specific binding of biotinylated heparin to HOMC was saturable at about 10 pg/ml, the Kp was estimated to about 0.15 pM. Biotinylated heparin bound rapidly to HOMC and reached a plateau within 60 min. Unlabeled heparin as well as pentosan polysulfate inhibited binding of biotinylated heparin in a dose-dependent fashion. These data demonstrate that heparin interacts with HOMC, and increases the fibrinolytic capacity in these cells by selectively increasing the production of tPA.

 

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