Involvement of neutrophils in thrombus formation in living mice
R Darbousset1, S Mezouar1, F Dignat-George1
1Inserm UMR-S1076, Aix Marseille Université, 27, boulevard Jean-Moulin, 13385 Marseille, France; Laboratoire d'hématologie, CHU Conception, 385, boulevard Baille, 13385 Marseille, France.
Abstract:
Thrombosis is one of the major causes of human death worldwide. Identification of the cellular and molecular mechanisms leading to thrombus formation is thus crucial for the understanding of the thrombotic process. To examine thrombus formation in a living mouse, new technologies have been developed. Digital intravital microscopy allows to visualize the development of thrombosis and generation of fibrin in real-time within living animal in a physiological context. This specific system allowed the identification of new cellular partners involved in platelet adhesion and activation. Furthermore, it improved, especially, the knowledge of the early phase of thrombus formation and fibrin generation in vivo. Until now, platelets used to be considered the sole central player in thrombus generation. However, recently, it has been demonstrated that leukocytes, particularly neutrophils, play a crucial role in the activation of the blood coagulation cascade leading to thrombosis. In this review, we summarized the mechanisms leading to thrombus formation in the microcirculation according to the method of injury in mice with a special focus on the new identified roles of neutrophils in this process.
Insights
Thrombosis, a leading cause of death, involves new insights into thrombus formation. Neutrophils, not just platelets, are key players in blood coagulation and thrombosis development.
Area of Science:
- Cardiovascular Biology
- Hematology
- Microcirculation Research
Background:
- Thrombosis is a major global cause of mortality.
- Understanding thrombus formation mechanisms is critical for developing effective treatments.
- Platelets were historically considered the primary drivers of thrombus generation.
Purpose of the Study:
- To review the mechanisms of thrombus formation in mouse microcirculation.
- To highlight the emerging roles of neutrophils in thrombosis.
- To discuss advancements in visualizing thrombus development in vivo.
Main Methods:
- Digital intravital microscopy for real-time visualization of thrombosis and fibrin generation in living mice.
- In vivo studies examining thrombus formation following different injury methods in the microcirculation.
- Review of recent literature identifying novel cellular and molecular players in thrombosis.
Main Results:
- Digital intravital microscopy enables real-time observation of thrombosis and fibrin formation in a physiological context.
- Identification of new cellular partners involved in platelet adhesion and activation.
- Demonstration of a crucial role for leukocytes, particularly neutrophils, in activating the coagulation cascade during thrombosis.
Conclusions:
- Neutrophils play a significant role in thrombus formation, challenging the long-held view of platelets as the sole central players.
- Advancements in intravital microscopy have significantly improved the understanding of early-stage thrombus formation and in vivo fibrin generation.
- Further research into the mechanisms of thrombosis, especially the role of neutrophils, is essential for improving patient outcomes.
