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Thrombin-Fibrin(ogen) Interactions, Host Defense and Risk of Thrombosis
Anne-Marije Hulshof1,2, H Coenraad Hemker3, Henri M H Spronk2
1Central Diagnostic Laboratory, Maastricht University Medical Centre, 6229 HX Maastricht, The Netherlands.
International Journal of Molecular Sciences
|April 3, 2021
Summary
Fibrinogen plays a dual role in thrombosis. While fibrin matrices promote clotting by protecting thrombin and activating immune cells, soluble fibrinogen may offer protection by reducing immune cell recruitment.
Area of Science:
- Biochemistry
- Hematology
- Immunology
Background:
- Fibrinogen is recognized as a risk factor for arterial and venous thrombosis.
- Its role extends beyond clot formation, involving complex interactions with thrombin and fibrin matrices.
- Fibrinogen influences hemostasis and vascular integrity through pleiotropic effects.
Purpose of the Study:
- To elucidate the dual role of fibrinogen in thrombosis, differentiating between soluble plasma fibrinogen and deposited fibrin matrices.
- To investigate the mechanisms by which fibrin matrices enhance procoagulant activity.
- To examine the contrasting effects of soluble fibrinogen and fibrin matrices on immune cell interactions and inflammation.
Main Methods:
- Analysis of thrombin generation experiments to observe fibrin's effect on thrombin adsorption and activity.
- Investigation of Mac-1 interactions between immobilized fibrin(ogen) and immune cells (monocytes/macrophages, neutrophils).
- Comparison of immune cell recruitment in the presence of soluble fibrinogen versus fibrin matrices.
Main Results:
- Fibrin matrices adsorb and protect thrombin from inhibitors like α2-macroglobulin, maintaining its activity and promoting coagulation.
- Immobilized fibrin(ogen) activates immune cells via Mac-1, inducing a pro-inflammatory response that stimulates coagulation.
- Soluble fibrinogen, in contrast, inhibits the recruitment of these immune cells.
Conclusions:
- Fibrin matrices contribute to a procoagulant state through direct thrombin protection and indirect immune system stimulation.
- High levels of soluble plasma fibrinogen may confer protection against thrombosis by suppressing immune cell activity.
- Future research should explore the in vivo balance between protective soluble fibrinogen and pro-thrombotic fibrin matrices in the context of thrombosis.
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