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. Author manuscript; available in PMC: 2013 Sep 15.
Published in final edited form as: J Immunol. 2012 Sep 15;189(6):2689–2695. doi: 10.4049/jimmunol.1201719

Figure 2. Putative stimuli and steps in NETosis.

Figure 2

A. Microbes and their products, immune complexes, autoantibodies, cytokines and other stimuli (IL8, TNF, and type I and II IFNs) can induce NETosis. Binding via TLRs, Fc receptors or complement receptors have been implicated in NETs’ induction. B. NETosis is initiated by binding of neutrophil surface receptors (R) to microbes or microbial breakdown products, inflammatory stimuli, or endogenous inducers. Binding to receptor(s) (exemplified in diagram as R1 and R2) induces ER calcium store release and opening of membrane channels that lead to cytoplasmic calcium increases. Elevated calcium stimulates PKC activity, phosphorylation of gp91phox, and assembly of functional NADPH Oxidase leading to reactive oxygen species (ROS) and nitric oxide (NO) production. Morphological changes observed during NETosis include breakdown of nuclear and granule membranes and the mixing of nuclear, granular and cytoplasmic contents. Deimination and proteolytic cleavage of histones may initiate before nuclear breakdown, and contribute to chromatin decondensation. A rupture in the plasma membrane allows the release of extracellular chromatin traps.