Neutrophil extracellular traps: is immunity the second function of chromatin? - PubMed (original) (raw)
Review
Neutrophil extracellular traps: is immunity the second function of chromatin?
Volker Brinkmann et al. J Cell Biol. 2012.
Abstract
Neutrophil extracellular traps (NETs) are made of processed chromatin bound to granular and selected cytoplasmic proteins. NETs are released by white blood cells called neutrophils, maybe as a last resort, to control microbial infections. This release of chromatin is the result of a unique form of cell death, dubbed "NETosis." Here we review our understanding of how NETs are made, their function in infections and as danger signals, and their emerging importance in autoimmunity and coagulation.
Figures
Figure 1.
Neutrophil morphology. Transmission electron microscopy (TEM) of a naive human neutrophil. This cell contains various types of granules, clearly visible in the cytoplasm, as well as a lobulated nucleus. The highly condensed heterochromatin (dark) is neatly marginalized to the edge of the nucleus, only interrupted by euchromatic areas close to nuclear pores that mostly line the nuclear membrane. The brighter euchromatin is mostly in the center of the lobules. This neutrophil comes from a female donor and one inactivated x chromosome can be found as an extranuclear stretch of heterochromatin (arrowhead). These structures are termed Barr bodies, and in neutrophils “drum sticks.” Bar, 2 µm.
Figure 2.
Bacteria caught in NETs. Scanning electron microscopy of human neutrophils incubated with Salmonella, a bacterium that causes typhoid fever and gastroenteritis. The bacteria are trapped in NETs. Bar, 1 µm.
Figure 3.
Schematic representation of the NETosis pathway. After stimulation of receptors (A), neutrophils adhere to the substrate (B) and mobilize granule components, namely NE and MPO (C). Granules are depicted as red circles. Histones in the nucleus get processed, and the intracellular membranes disintegrate. Finally, the cell membrane ruptures, and the mixture of cytoplasm and nucleoplasm gets expelled to form NETs (D).
Figure 4.
Visualizing NETs using chromatin antibodies or DNA-intercalating dyes. Human neutrophils were activated in vitro and then processed for immunofluorescence. An antibody directed against the subnucleosomal complex of H2A, H2B, and DNA stains intact, compact chromatin only weakly, but reacts strongly with relaxed chromatin in the NETs (A, red in D). In contrast, DNA-intercalating dyes provide the brightest staining at sites of high DNA concentrations, as is the case in compact nuclei, whereas NETs are stained rather weakly (A, Hoechst 33342; blue in D). (C, green in D) The granular marker NE, which can be observed in granules in cells that are not yet activated, as well as in NETs. A projection of confocal z-stack is shown. Bar, 10 µm.
Figure 5.
NETs are abundant in Pus. Pus consists of numerous neutrophils in various stages of NETosis (arrowheads) surrounded by NETs. Semithin cryosection of pus from a Molluscum contagiosum lesion stained for NE (green) and chromatin (red). Bar, 20 µm.
Similar articles
- Neutrophil Extracellular Traps: The Biology of Chromatin Externalization.
Sollberger G, Tilley DO, Zychlinsky A. Sollberger G, et al. Dev Cell. 2018 Mar 12;44(5):542-553. doi: 10.1016/j.devcel.2018.01.019. Dev Cell. 2018. PMID: 29533770 Review. - NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin decondensation and nuclear envelope rupture.
Thiam HR, Wong SL, Qiu R, Kittisopikul M, Vahabikashi A, Goldman AE, Goldman RD, Wagner DD, Waterman CM. Thiam HR, et al. Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7326-7337. doi: 10.1073/pnas.1909546117. Epub 2020 Mar 13. Proc Natl Acad Sci U S A. 2020. PMID: 32170015 Free PMC article. - Receptor-Mediated NETosis on Neutrophils.
Chen T, Li Y, Sun R, Hu H, Liu Y, Herrmann M, Zhao Y, Muñoz LE. Chen T, et al. Front Immunol. 2021 Nov 4;12:775267. doi: 10.3389/fimmu.2021.775267. eCollection 2021. Front Immunol. 2021. PMID: 34804066 Free PMC article. Review. - Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality.
Remijsen Q, Kuijpers TW, Wirawan E, Lippens S, Vandenabeele P, Vanden Berghe T. Remijsen Q, et al. Cell Death Differ. 2011 Apr;18(4):581-8. doi: 10.1038/cdd.2011.1. Epub 2011 Feb 4. Cell Death Differ. 2011. PMID: 21293492 Free PMC article. Review. - Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease.
Klopf J, Brostjan C, Eilenberg W, Neumayer C. Klopf J, et al. Int J Mol Sci. 2021 Jan 8;22(2):559. doi: 10.3390/ijms22020559. Int J Mol Sci. 2021. PMID: 33429925 Free PMC article. Review.
Cited by
- The CAMKK/AMPK Pathway Contributes to _Besnoitia besnoiti_-Induced NETosis in Bovine Polymorphonuclear Neutrophils.
Conejeros I, Velásquez ZD, Rojas-Barón L, Espinosa G, Hermosilla C, Taubert A. Conejeros I, et al. Int J Mol Sci. 2024 Aug 2;25(15):8442. doi: 10.3390/ijms25158442. Int J Mol Sci. 2024. PMID: 39126009 Free PMC article. - Suppressive effect of resveratrol, catechin and their conformationally constrained analogs on neutrophil extracellular trap formation by HL-60-derived neutrophils.
Ohinata H, Phimarn W, Mizuno M, Obama T, Fukuhara K, Makiyama T, Watanabe Y, Itabe H. Ohinata H, et al. J Clin Biochem Nutr. 2024 Jul;75(1):17-23. doi: 10.3164/jcbn.23-80. Epub 2024 Mar 5. J Clin Biochem Nutr. 2024. PMID: 39070531 Free PMC article. - Neutrophil PAD4 Expression and Its Pivotal Role in Assessment of Alcohol-Related Liver Disease.
Rycyk-Bojarzynska A, Kasztelan-Szczerbinska B, Cichoz-Lach H, Surdacka A, Rolinski J. Rycyk-Bojarzynska A, et al. Int J Mol Sci. 2024 Jul 11;25(14):7597. doi: 10.3390/ijms25147597. Int J Mol Sci. 2024. PMID: 39062840 Free PMC article. - IL-8 Induces Neutrophil Extracellular Trap Formation in Severe Thermal Injury.
Asiri A, Hazeldine J, Moiemen N, Harrison P. Asiri A, et al. Int J Mol Sci. 2024 Jun 29;25(13):7216. doi: 10.3390/ijms25137216. Int J Mol Sci. 2024. PMID: 39000323 Free PMC article. - From inside to outside: exploring extracellular antimicrobial histone-derived peptides as multi-talented molecules.
Muñoz-Camargo C, Cruz JC. Muñoz-Camargo C, et al. J Antibiot (Tokyo). 2024 Sep;77(9):553-568. doi: 10.1038/s41429-024-00744-0. Epub 2024 Jun 13. J Antibiot (Tokyo). 2024. PMID: 38871806 Free PMC article. Review.
References
- Altincicek B., Stötzel S., Wygrecka M., Preissner K.T., Vilcinskas A. 2008. Host-derived extracellular nucleic acids enhance innate immune responses, induce coagulation, and prolong survival upon infection in insects. J. Immunol. 181:2705–2712 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources