How Neutrophil Extracellular Traps Become Visible

Figure 2

Mechanisms of NET formation: vital versus suicidal NETosis. (a)–(d) The “suicidal” NETosis starts after a stimulation by, for example, PMA, IL-8, or various microbial pathogens in a NADPH-oxidase-dependent matter and leads to NET release within 1 to 4 h. Translocation of MPO, elastase, and LL-37 to the nucleus leads to the nuclear decondensation and disruption of the nuclear membrane [78, 79]. Subsequently, the content of the nucleus mixes with the granular as well as cytosolic proteins. Finally, the outer membrane ruptures and NETs are released by the activated neutrophils into the extracellular space. (e)-(f) The “vital” NETosis has been described to be a rapid release of NETs (5–60 min). It can be induced by a TLR-4-mediated platelet activation and its interaction with CD11a on neutrophils [38]. Furthermore, an activation via complement receptor 3 (CR3) and TLR-2 has also been shown in the presence of Gram-positive bacteria, for example, Staphylococcus (S.) aureus [35]. The nucleus becomes rounded and decondensed (f). Vesicles with nuclear DNA are formed (g) and NETs are released via nuclear budding (h). The outer membrane remains intact upon NET release and the anuclear neutrophil retains the ability to multitask [35] (adapted [36]).