Neutrophil Extracellular Trap Formation Is Independent of De Novo Gene Expression.

Gabriel Sollberger,Borko Amulic,Arturo Zychlinsky,Dominik Hartl

doi:10.1371/journal.pone.0157454

Gabriel Sollberger, Borko Amulic + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0157454

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Journal: PloS one	Publication Date: Jun 16, 2016
Citations: 39	License type: CC BY 4.0

Affiliation: Max Planck Institute for Infection Biology

Abstract

Neutrophils are essential innate immune cells whose responses are crucial in the clearance of invading pathogens. Neutrophils can respond to infection by releasing neutrophil extracellular traps (NETs). NETs are formed of chromatin and specific granular proteins and are released after execution of a poorly characterized cell death pathway. Here, we show that NET formation induced by PMA or Candida albicans is independent of RNA polymerase II and III-mediated transcription as well as of protein synthesis. Thus, neutrophils contain all the factors required for NET formation when they emerge from the bone marrow as differentiated cells.

Highlights

Neutrophils are essential for innate immune defense because they are directly antimicrobial and can shape adaptive immunity [1, 2]
We first confirmed the activity of our inhibitors and titrated the minimal concentrations required for inhibition in neutrophils
To accomplish this we used as our readout the transcription and translation of Macrophage Inflammatory Protein (Mip)-1α, a chemokine known to be produced de novo in response to LPS [13] (Fig 1A, S1A Fig)

Summary

Introduction

Neutrophils ( called polymorphonuclear leukocytes, PMNs) are essential for innate immune defense because they are directly antimicrobial and can shape adaptive immunity [1, 2]. During infections neutrophils are rapidly recruited to inflammatory sites where they activate different antimicrobial programs, such as phagocytosis, production of reactive oxygen species (ROS), degranulation or the formation of neutrophil extracellular traps (NETs). NETs are released by PMNs after the activation of a specialized cell death pathway and consist of chromatin bound to cytoplasmic proteins [3, 4, 5]. Many NET inducers trigger MAP kinase signaling [6], activate NADPH oxidase (Nox2) and involve the subsequent production of ROS. This leads to granule rupture mediated by a protein complex called “azurosome”, translocation of neutrophil elastase (NE) to the nucleus, chromatin decondensation and NET production [7]. NETs are dyresgulated in several auto-immune and inflammatory diseases, making them an important target for potential therapeutic interventions [5]

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