Table 1.
Comparisons of NETosis mechanisms.
| Type of NETosis | Vital | Mitochondrial | Suicidal | Caspase Dependent |
|---|---|---|---|---|
| Stimuli | LPS [65,66] | GM-CSF [78], C5a [78], RNP ICs [79] | PMA [4,5,60], LPS [5], viral glycoproteins [69,70,71], C. albicans [80], C5a [68], IL-8 [5], crystalline particles [61], activated platelets [62], ANCA [63], TNFα [67] | Cytosolic LPS [75] |
| Receptors | TLR2 [65] | TLR7 [81] | TLR4 [70], TLR7 [69,71], TLR8 [69,71], C5aR1 [68], TNFαR | |
| Adaptors | C3 [65] | PKC [72] GSDMD [59], MLKL/RIPK3 (stimulus dependent) [60,61,62,63] | Caspase-11, GSDMD [75] | |
| Cascades | Raf-MEK-ERK [73], ERK and p38 MAPK [70], AKT [82] | |||
| Oxidant reliance | ROS independent [66] | ROS dependent [78,79] | ROS production [56,57,70,83] | |
| Components released | DNA, histones and dense granules [65,66] | Mitochondrial DNA | DNA, histones and proteins from primary [5,74,84,85], secondary and tertiary granules [5] | DNA and histones [75] |
| Downstream pathways activated | TLR9 [86], NFκB [87], cGAS-STING, Type I IFN [79]; | Complement cascade [63], IL-17 |
AKT: protein kinase B; ANCA: anti-neutrophil cytoplasmic antibody; cGAS-STING: cyclic GMP–AMP synthase and stimulator of interferon genes; EC: extracellular; DNA: deoxyribonucleic acid; ERK: extracellular signal-regulated protein kinase; GM-CSF: granulocyte-macrophage colony-stimulating factor; GSDMD: gasdermin D; IFN: interferon; IL: interleukin; LPS: lipopolysaccharide; MAPK: mitogen activated protein kinase; MEK: ERK kinase; MLKL: mixed lineage kinase domain-like; NET: neutrophil extracellular trap; NFκB: nuclear factor kappa B; PKC: protein kinase C; PMA: phorbol 12-myristate 13-acetate; Raf: rapidly accelerated fibrosarcoma proto-oncogene serine/threonine-protein kinase; RIPK3: receptor-interacting serine/threonine kinase 3; RNP IC: ribonucleoprotein immune complex; ROS: reactive oxygen species; TLR: Toll-like receptor; TNFα: tumour necrosis factor α.