Characterization and visualization of platelet-neutrophil interaction during thrombus formation

• Applicant: Dr. Tobias Fuchs
• Subject Area: Hematology, Oncology
• Term: from 2008 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 68955829

As a first response to vascular injury, platelets are captured and activated at injured sites. Activated platelets trigger recruitment and activation of other platelets as well as leukocytes. Platelets together with leukocytes mediate the growth of the thrombus and finally plug the endothelial damage. Recently activated platelets were shown to induce neutrophil extracellular traps (NETs) in a murine model of sepsis. NETs emerge from activated neutrophils, are composed of chromatin decorated with granular proteins and ensnare microbes.I propose that first, neutrophils are recruited to thrombi; second, upon interaction with activated platelets NETs are induced; third, NETs are important for thrombus growth and stability. In flow chamber experiments I will identify molecular mechanisms of platelet-neutrophil-interactions causing NET formation. In murine models of thrombosis I will visualize and characterize NET formation in real time in life animals by intravital-microscopy. I hypothesize that NETs are crucial for thrombus stability and promote thrombus growth which ultimately obstructs the blood flow and leads to pathogenic thrombosis. Thrombosis is linked to myocardial infarction, ischemic stroke, deep vein thrombosis, cancer as well as disseminated intravascular coagulation, a condition mainly associated with sepsis. These conditions are distributed world wide and a main cause for mortality.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Denisa D. Wagner, Ph.D.