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PXD027055

PXD027055 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEarly and late processes driving NET formation, and the autocrine/paracrine role of endogenous RAGE ligands
DescriptionNeutrophil 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.
HostingRepositoryPRIDE
AnnounceDate2021-10-12
AnnouncementXMLSubmission_2021-10-12_05:34:53.151.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFrancois-Michel Boisvert
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-07-01 23:31:49ID requested
12021-10-12 05:34:53announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Neutrophil, NET formation, activation, inflammation, autoimmunity
Contact List
Patrick McDonald
contact affiliationDepartment of Medecine, Service of Pneumology, Université de Sherbrooke
contact emailPatrick.McDonald@usherbrooke.ca
lab head
Francois-Michel Boisvert
contact affiliationUniversité de Sherbrooke
contact emailfm.boisvert@usherbrooke.ca
dataset submitter
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Dataset FTP location
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