Figure 3.

Balancing apoptosis versus NETosis. In response to numerous inflammatory stimuli, including combinations of inflammatory cytokines, pathogens, immune complexes, and extracellular membrane (ECM) components, neutrophils can be activated to undergo either NETosis or apoptosis. We propose that the balance between these two outcomes is a function of the strength or presentation of the stimulus—neutrophils that are highly primed by cytokines and subsequently exposed to opsonized microbes may undergo apoptosis, whereas weaker stimuli may lead to NETosis. Whether neutrophils undergo NETosis or apoptosis dictates the subsequent immune responses. NETosis tends to be pro-inflammatory and prothrombotic and to lead to the release of novel self-antigens, such as deiminated proteins, which stimulate autoimmunity. By contrast, apoptosis is anti-inflammatory, in that it leads to the promotion of M2 macrophage development associated with wound healing and tissue repair processes.