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Modulation of protein C inhibitor activity
L L Neese1, C W Pratt, F C Church
1Department of Pathology, University of North Carolina at Chapel Hill, School of Medicine 27599.
Summary
Protein C inhibitor (PCI) activity is influenced by endothelial cell substances. These factors modulate PCI
Area of Science:
- Biochemistry
- Molecular Biology
- Vascular Biology
Background:
- Protein C inhibitor (PCI) is a serpin that inhibits proteinases.
- PCI's activity is modulated by heparin and substances interacting with the vascular endothelium.
Purpose of the Study:
- To investigate how endothelial cell/basement membrane substances affect PCI interactions with thrombin and activated protein C (APC).
Main Methods:
- Studied the effects of antithrombin-heparin, thrombomodulin, vitronectin, and leukocyte elastase on PCI activity.
- Assessed inhibition rates of PCI-thrombin and PCI-APC interactions under various conditions.
Main Results:
- Thrombomodulin accelerated PCI inhibition of thrombin and APC.
- Vitronectin decreased PCI inhibition rates in the presence of low heparin concentrations.
- Leukocyte elastase inactivated PCI, a reaction accelerated by heparin.
Conclusions:
- Endothelial cell/basement membrane substances modulate PCI activity similarly to other heparin-binding serpins.
- PCI's interactions are influenced by its binding affinity and the presence of heparin.