Plasminogen activator-specific inhibitors produced by human monocytes/macrophages
The Journal of Experimental Medicine
|February 1, 1987
Summary
Human monocytes produce two forms of plasminogen activator inhibitors (PAIs) that inhibit urokinase-type plasminogen activator (uPA). These PAIs are distinct from plasma protease inhibitors and related to placental PAI-2.
Area of Science:
- Biochemistry
- Cell Biology
- Immunology
Background:
- Human monocytes/macrophages synthesize plasminogen activator inhibitors (PAIs).
- PAIs form covalent complexes with urokinase-type plasminogen activator (uPA).
Purpose of the Study:
- Characterize two functionally and antigenically related PAIs produced by U 937 cells.
- Investigate the synthesis, properties, and relationship of these PAIs to known inhibitors.
Main Methods:
- U 937 cell culture and treatment with phorbol myristate acetate (PMA).
- Biosynthetic labeling and characterization of PAIs (Mr, pI).
- Complex formation and dissociation studies with 125I-uPA.
- Antigenic comparison with placental PAI-2.
Main Results:
- Two distinct PAI forms identified: a constitutive intracellular Mr 40,000 PAI and a PMA-induced secreted Mr 50,000-65,000 glycosylated PAI.
- Both PAIs are synthesized by U 937 cells and human peripheral blood monocytes/macrophages.
- PAI-uPA complexes involve an ester bond and are dissociated by ammonium hydroxide.
- These PAIs are antigenically related to human placental PAI-2 and distinct from plasma protease inhibitors.
Conclusions:
- U 937 cells and human monocytes/macrophages produce two distinct, antigenically related PAIs.
- These PAIs play a role in regulating uPA activity and are similar to PAI-2.
- The characterization provides insights into the plasminogen activation system in monocytes/macrophages.
