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A prothrombinase complex of mouse peritoneal macrophages
U Lindahl1, G Pejler, J Bøgwald
1Department of Veterinary Medical Chemistry, Biomedical Center, Uppsala, Sweden.
Archives of Biochemistry and Biophysics
|August 15, 1989
Summary
Mouse macrophages activate prothrombin into thrombin via Factor Xa on their surface. This process is modulated by heparin and its oligosaccharides, impacting coagulation during inflammation.
Area of Science:
- Biochemistry
- Cell Biology
- Immunology
Background:
- Macrophages play a role in inflammatory conditions.
- Coagulation factors can be activated on cell surfaces.
Purpose of the Study:
- To investigate the mechanism of prothrombin activation by mouse peritoneal macrophages.
- To determine the role of Factor Xa in macrophage-mediated thrombin generation.
- To explore the modulatory effects of heparin and its oligosaccharides on this process.
Main Methods:
- In vitro incubation of prothrombin with mouse peritoneal macrophages.
- Assay of thrombin-like enzyme activity using luminogenic peptide substrate S-2621.
- Analysis of prothrombinase activity localization and sensitivity to Triton X-100 and warfarin.
- Investigation of thrombin inhibition by antithrombin and modulation by heparin and heparin oligosaccharides.
Main Results:
- Macrophages generated a thrombin-like enzyme from prothrombin, mediated by Factor Xa.
- Prothrombinase activity was associated with the cell surface and sensitive to detergent and warfarin.
- Heparin accelerated thrombin inhibition by antithrombin, while specific heparin oligosaccharides inhibited thrombin formation by promoting Factor Xa inactivation.
Conclusions:
- Macrophage-associated Factor Xa catalyzes prothrombin cleavage, generating thrombin.
- Heparin and its oligosaccharides can modulate macrophage prothrombinase activity, suggesting a role in regulating local coagulation during inflammation.