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Antithrombin inactivation by neutrophil elastase requires heparin
R E Jordan1, R M Nelson, J Kilpatrick
1Department of Physiology, Cutter Biological, Miles Inc., Berkeley, California.
The American Journal of Medicine
|September 11, 1989
Summary
In thrombotic states, heparin may paradoxically inactivate antithrombin, a key clotting inhibitor. This novel mechanism involves neutrophil elastase cleaving the heparin-antithrombin complex, potentially reducing antithrombin levels during inflammation.
Area of Science:
- Biochemistry
- Hematology
- Vascular Biology
Background:
- Circulating antithrombin levels decline in thrombotic states, potentially due to endothelial activity.
- Heparin, an anticoagulant, may have paradoxical effects in pathological conditions.
Purpose of the Study:
- To investigate a novel mechanism for antithrombin inactivation in pathological conditions.
- To explore the role of heparin and neutrophil elastase in antithrombin dysfunction.
Main Methods:
- In vitro studies examining heparin-antithrombin interactions.
- Assessing the effect of neutrophil elastase on the heparin-antithrombin complex.
- Investigating the binding affinity of neutrophil elastase to heparin.
Main Results:
- Heparin-dependent cleavage of antithrombin by neutrophil elastase rendered it nonfunctional.
- This inactivation occurred specifically within the heparin-antithrombin complex.
- Neutrophil elastase demonstrated strong binding to heparin and heparin-like materials.
Conclusions:
- A novel mechanism suggests neutrophil elastase inactivates antithrombin in the presence of heparin.
- This process may occur on the vascular surface, localized away from circulating inhibitors.
- This localized antithrombin inactivation could contribute to thrombotic events in inflammatory diseases.