Intracellular signaling involved in the programmed neutrophil cell death leading to the release of extracellular DNA traps in thrombus formation

Abstract

The formation of extracellular DNA traps by neutrophils, or NETs (neutrophil extracellular traps) plays an essential role in many pathological processes related to hematological, oncological, and immunological diseases. This mechanism of the programmed cell death of neutrophils and other leukocytes appears to be also involved in the pathogenesis of thrombosis and thrombotic complications of a variety of disorders. In this review, we discuss the pathways of intracellular signaling leading to neutrophil activation in thrombosis and hemostasis. Even though the biochemical reactions in a cell are quite well investigated, the regulation of activity of specific proteins involved in NETosis, such as NADPH oxidase (NOX) and protein-arginine deiminase (PAD4), requires further investigation. Current approaches to the pharmacological modulation of NETosis are also specifically addressed here.