Novel cell death program leads to neutrophil extracellular traps

TLDR

Neutrophil extracellular traps (NETs) are chromatin‑based structures that bind and kill microorganisms. The authors identify a ROS‑dependent, NADPH oxidase‑driven cell death pathway that produces NETs, distinct from apoptosis and necrosis, and is defective in chronic granulomatous disease patients.

Abstract

Neutrophil extracellular traps (NETs) are extracellular structures composed of chromatin and granule proteins that bind and kill microorganisms. We show that upon stimulation, the nuclei of neutrophils lose their shape, and the eu- and heterochromatin homogenize. Later, the nuclear envelope and the granule membranes disintegrate, allowing the mixing of NET components. Finally, the NETs are released as the cell membrane breaks. This cell death process is distinct from apoptosis and necrosis and depends on the generation of reactive oxygen species (ROS) by NADPH oxidase. Patients with chronic granulomatous disease carry mutations in NADPH oxidase and cannot activate this cell-death pathway or make NETs. This novel ROS-dependent death allows neutrophils to fulfill their antimicrobial function, even beyond their lifespan.