[Frontiers in Bioscience 11, 59-80, January 1, 2006]

Blood coagulation-dependent inflammation. Coagulation-dependent inflammation and inflammation-dependent thrombosis

Svetlana Strukova

Department of Human and Animal Physiology, Faculty of Biology, Lomonosov Moscow State University, Moscow, 119992, Russia

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Platelets and endothelium are the source of proteins for coagulation and inflammation
3.1. Endothelial cell adhesion molecules
3.2. Pletelet glycoproteins for cell adhesion, aggreration and inflammation
4.Tissue factor as trigger of blood coagulation
4.1.TF structure and functions
4.2. Generation of hemostatic serine proteinases
4.3. Regulation of blood coagulation and inflammation by TFPI
5. Functions of hemostatic serine proteinases in inflammation
5.1. Thrombin signalling pathways in inflammation
5.2. TF/FVIIa/Xa- induced inflammation
5.3.Termination of PAR signaling.
6. Control of inflammation by natural anticoagulant pathways
6.1. Antiinflammatory properties of protein C system
6.2. Endothelial protein C receptor as regulator of coagulation and inflammation.
6.3. Antiinflammatory properties of antithrombin
7. The new approach to correction of TF/VIIa/Xa-dependented thrombosis and conjugated prosseses
8. Summary and perspective
9. Acknowledgement

10.References

1. ABSTRACT

Hemostatic serine proteinases -thrombin, Factor VIIa , Factor Xa , play the central role in blood coagulation and thrombosis. Activation of coagulation and generation of active proteinases is initiated by tissue factor (TF) that is expressed by cells of the innate immune system and endothelial cells after tissue damage and cell activation induced by trauma, infection, hypoxia and other cell injury. Coagulation and inflammation are the essential part of the defensive host response . These processes have several connecting points account for the associate and/or the interaction between coagulation and inflammation pathways. The first link between these processes is endothelium, which after damage expresses the adhesive proteins (vWF,P-selectin),inductors and receptors, involved in both coagulation and inflammation. The second link is platelets, which stored in and after activation release proteins with procoagulant and proinflammatory properties. The third link is the serine proteinases, which produced for blood coagulation and activate via its specifical receptors - PARs ( proteinase activated receptors) the cells of both coagulation and inflammation system thereby controlling these prosesses. The generation of these proteinases is initiated by tissue factor (TF) which triggers blood coagulation at sites of tissue injury by selective binding of FVIIa. TF/VIIa complexes with substrate - FX that is activated to FXa. TF/VIIa/Xa can activate both the inflammatory responses of endothelial and other cells and also blood coagulation through stimulation of thrombin generation. This review summarizes the latest data on the blood coagulation activation that include generation of active surface for coagulation, generation of hemostatic serine proteinases and its role as signalling molecules that via PARs and other receptors involved in regulation and control of the interaction of blood coagulation and inflammation and illustrates the potential for therapeutic intervention.