Single Cell Biology

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Neutrophil Extracellular Trap Formation: A Single Cell Event?

Lena Völlger and Maren von Köckritz-Blickwede

In 2004, neutrophil extracellular traps (NETs) have been described as fundamental immune defense of neutrophils against various microbes. Since that time publications are increasing that characterize the stimuli and cellular mechanisms which can activate the cells to release NETs. However, it is still not entirely clear whether NET formation starts as a single cell event, that spreads by cell to cell communication or if neighboring cells undergo NET formation simultaneously caused by a common trigger. Using immunofluorescence microscopy, we here show that at lower cell density only single cells were detected that released NET structures. However, the higher the cell density, the higher was the x-fold-increase of NET formation in PMA stimulated cells compared to unstimulated cells. This might give a hint that NET formation might start as a single cell event but is able to spread due to cell communication. To fully understand the mechanisms mediating NET formation, future experiments should focus on single cell analysis to characterize the detailed cellular events that mediate formation of NETs in single cells within a population and to differentiate the signaling process that leads to NET formation in contrast to other antimicrobial strategies as phagocytosis or degranulation.