PXD027055-1

PXD027055 is an original dataset announced via ProteomeXchange.

Title	Early and late processes driving NET formation, and the autocrine/paracrine role of endogenous RAGE ligands
Description	Neutrophil extracellular trap (NET) formation has emerged as an important response against various pathogens; it also plays a role in chronic inflammation, autoimmunity, and cancer. Despite a growing understanding of the mechanisms underlying NET formation, much remains to be elucidated. We previously showed that in human neutrophils activated with different classes of physiological stimuli, NET formation features both early and late events that are controlled by discrete signaling pathways. However, the nature of these events has remained elusive. We now report that PAD4 inhibition only affects the early phase of NETosis, as do distinct signaling intermediates (TAK1, MEK, p38 MAPK). Accordingly, the inducible citrullination of residue R2 on histone H3 is an early neutrophil response that is regulated by these kinases; other arginine residues on histones H3 and H4 do not seem to be citrullinated. Conversely, chromatin decondensation is a belated event in NET formation, that is impaired by the inhibition of most signaling pathways known to control the phenomenon. We additionally show that neutrophils can condition themselves to be poised for rapid NET formation, and that this represents another late process. Similarly, activated neutrophils release a number of endogenous proteic factors that promote and largely mediate NET generation, and this is yet another late process. Our data shed new light on the cellular processes underlying NET formation, and unveil some unsuspected facets of the phenomenon. In view of the involvement of NETs in both homeostasis and several pathologies, our findings are of broad relevance.
HostingRepository	PRIDE
AnnounceDate	2021-10-12
AnnouncementXML	Submission_2021-10-12_05:34:53.151.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Francois-Michel Boisvert
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-01 23:31:49	ID requested
⏵ 1	2021-10-12 05:34:53	announced

Dataset with its publication pending

submitter keyword: Neutrophil, NET formation, activation, inflammation, autoimmunity

Patrick McDonald
contact affiliation	Department of Medecine, Service of Pneumology, Université de Sherbrooke
contact email	Patrick.McDonald@usherbrooke.ca
lab head
Francois-Michel Boisvert
contact affiliation	Université de Sherbrooke
contact email	fm.boisvert@usherbrooke.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027055
     1. Label: PRIDE project
     2. Name: Early and late processes driving NET formation, and the autocrine/paracrine role of endogenous RAGE ligands