Abstract
Plasminogen activator inhibitor 2 (PAI-2) is a major product of activated human monocytes. Here we show that monocytes inhibited u-PA- but not t-PA-mediated fibrinolysis, by secreting PAI-2 into an overlying fibrin clot. Extracts of arterial and venous human thrombi were found to contain active PAI-2. PAI-2 was cross-linked to fibrin in a reaction catalyzed by two major transglutaminases (TG), tissue TG and factor XIII. The activity of PAI-2 was not affected by such cross-linking. Cross-linking of PAT-2 to fibrin was inhibited by Tridegin, a specific inhibitor of TG, and also by EDTA and iodoacetamide, The use of competitive peptides mimicking the loop between helices C and D of PAI-2 identified Gin 83 and 86 as residues important in crosslinking. This study defines a mechanism by which PAI-I, is localized to fibrin, where it acts as an effective inhibitor of u-PA-mediated fibrinolysis.
Original language | English |
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Pages (from-to) | 96-103 |
Number of pages | 8 |
Journal | Journal of Thrombosis and Haemostasis |
Volume | 81 |
Publication status | Published - 1999 |
Keywords
- TUMOR-NECROSIS-FACTOR
- PERIPHERAL-BLOOD MONOCYTES
- FACTOR-XIIIA
- HAEMENTERIA-GHILIANII
- PEPTIDIC INHIBITOR
- ENDOTHELIAL-CELLS
- IN-VITRO
- TYPE-2
- LINKING
- TRANSGLUTAMINASE