Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps

Journal of Cell Biology - Tập 191 Số 3 - Trang 677-691 - 2010
Venizelos Papayannopoulos1, Kathleen D. Metzler1, Abdul Hakkim1, Arturo Zychlinsky1
1Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin 10117, Germany

Tóm tắt

Neutrophils release decondensed chromatin termed neutrophil extracellular traps (NETs) to trap and kill pathogens extracellularly. Reactive oxygen species are required to initiate NET formation but the downstream molecular mechanism is unknown. We show that upon activation, neutrophil elastase (NE) escapes from azurophilic granules and translocates to the nucleus, where it partially degrades specific histones, promoting chromatin decondensation. Subsequently, myeloperoxidase synergizes with NE in driving chromatin decondensation independent of its enzymatic activity. Accordingly, NE knockout mice do not form NETs in a pulmonary model of Klebsiella pneumoniae infection, which suggests that this defect may contribute to the immune deficiency of these mice. This mechanism provides for a novel function for serine proteases and highly charged granular proteins in the regulation of chromatin density, and reveals that the oxidative burst induces a selective release of granular proteins into the cytoplasm through an unknown mechanism.

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