Neutrophil Extracellular Traps and von Willebrand Factor in Thrombosis

For many years, my lab has been studying the interplay between inflammation and thrombosis. These processes occur together, stimulate each other and share cellular and molecular components. The latest example of a common functional component is neutrophil extracellular traps (NETs). NETs are chromatin released together with toxic granular components from highly stimulated neutrophils. Originally found to trap/sequester invading pathogens, they were soon also seen to be part of sterile inflammatory and thrombotic processes. They interact with von Willebrand factor (VWF), which is also involved in platelet and leukocyte recruitment and is crucial for venous thrombus development after inferior vena cava stenosis. It is possible that NETs and VWF work together and cleavage of either by DNase 1 or ADAMTS13 is beneficial in ischemia/reperfusion injury. This will be discussed together with the role of NETs and the enzyme that generates them (PAD4) in animal models of deep vein thrombosis, myocardial infarction and in physiological wound healing. Interestingly, we observed that various cancers in mice prime neutrophils for NETosis. This causes cancer-associated thrombosis, and the production of NETs may affect tumor biology.