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Review
. 2012 Sep 3;198(5):773-83.
doi: 10.1083/jcb.201203170.

Neutrophil extracellular traps: is immunity the second function of chromatin?

Volker Brinkmann  1 , Arturo Zychlinsky
Affiliations
Review

Neutrophil extracellular traps: is immunity the second function of chromatin?

Volker Brinkmann et al. J Cell Biol. .

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.

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Figures

Figure 1.
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.
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.
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.
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.
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.
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