Cell Biology

Caught in the NET

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Science  26 Jan 2007:
Vol. 315, Issue 5811, pp. 438
DOI: 10.1126/science.315.5811.438a

When circulating neutrophils are challenged by microbes, they can transform themselves into neutrophil extracellular traps or NETs, which are constructed out of chromatin (from the nucleus) and granule proteins (from the cytoplasm). These NETs grab hold of and sequester bacteria—and in doing so, they keep them within the range of antimicrobial enzymes and peptides.

Fuchs et al. show that this process involves a new type of cell death program. After neutrophils are stimulated, the normal segregation of chromatin into regions that are actively transcribing genes and those that are inactive disappears, and the nuclei become deformed. Subsequently, intracellular membranes, including the nuclear envelope and also granule membranes, disintegrate; this leads to the mixing and assembly of the NET components, which are then released from the dying cell as its plasma membrane ruptures. This sequence of cell death is distinct from other known forms of programmed cell death and appears to involve reactive oxygen species (superoxide and peroxide) that are produced by NADPH oxidase. Chronic granulomatous disease patients are deficient in this enzyme and cannot make NETs, which may explain in part why they suffer recurrent infections. Thus, even with their last breath, neutrophils contribute to the fight against invasive microbes. — SMH

J. Cell Biol. 176, 231 (2007).

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