The power from within – understanding the driving forces of neutrophil extracellular trap formation

Neutrophil extracellular traps (NETs) are one of the most intriguing discoveries in immunological research of the past few years. After their first description in 2004, the number of research articles on how NETs affect immunodefense, and also how they contribute to an ever-growing number of diseases, has skyrocketed. However, tempting as it may seem to plunge into pharmaceutical approaches to tamper with NET formation, our understanding of this complex process is still incomplete. Important concepts such as the context-dependent dual functions of NETs, in that they are both inflammatory and anti-inflammatory, or the major intra- and extracellular forces driving NET formation, are only emerging. In this Review, we summarize key aspects of our current understanding of NET formation (also termed NETosis), emphasize biophysical aspects and focus on three key principles - rearrangement and destabilization of the plasma membrane and the cytoskeleton, alterations and disassembly of the nuclear envelope, and chromatin decondensation as a driving force of intracellular reorganization.