PXD078688-1

PXD078688 is an original dataset announced via ProteomeXchange.

Title	A feedback loop sustaining neutrophil extracellular trap formation involves S100 proteins, histones, TLR2 and RAGE, and is restrained by albumin
Description	Neutrophil extracellular trap (NET) generation must be tightly controlled as this essential antimicrobial response can also cause tissue damage and contribute to various pathologies. We previously described that neutrophils undergoing NET formation release endogenous mediators that feed back on the cells via the RAGE receptor to drive the response. We now identify S100 proteins and histones as prominent endogenous NET inducers. Mass spectrometry analyses of culture supernatant from NETing neutrophils revealed the presence of seven species of S100 proteins and 10 histone variants, all of which could bind to RAGE. In addition, endogenous NET inducers were found to act via TLR2 since antagonism of the receptor for up to 3 h post-stimulation hindered NET formation elicited by various classes of physiological stimuli. By comparison, antagonism of TLR4 did not affect NET generation. Conversely, we show that serum or equivalent albumin concentrations restrain NET formation by sequestering endogenous NET inducers. Serum depleted of albumin indeed loses its ability to prevent NET formation; likewise, the belated addition of HSA to culture medium blocks NET generation. Prior exposure to serum or albumin renders endogenous NET inducers unable to trigger the response; mass spectrometry analysis confirmed that albumin captures S100 proteins. Collectively, our data unveil a feedback loop of NET formation involving endogenous S100 proteins and histones, acting through RAGE and/or TLR2, that can be physiologically counteracted by albumin.
HostingRepository	PRIDE
AnnounceDate	2026-06-29
AnnouncementXML	Submission_2026-06-28_16:28:49.240.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vanessa de Carvalho Oliveira
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-21 13:18:33	ID requested
⏵ 1	2026-06-28 16:28:50	announced

10.3389/fimmu.2026.1774475;

de Carvalho Oliveira V, Mazur M, McDonald PP, A feedback loop sustaining neutrophil extracellular trap formation involves S100 proteins, histones, TLR2 and RAGE, and is restrained by albumin. Front Immunol, 17():1774475(2026) [pubmed]

submitter keyword: TLR2, endogenous factors, RAGE, histones, human serum albumin, neutrophil extracellular traps, S100 proteins,DAMPs

Patrick McDonald
contact affiliation	Pulmonary Division, CRCHUS, Universite de Sherbrooke, Sherbrooke, QC, Canada.
contact email	patrick.mcdonald@usherbrooke.ca
lab head
Vanessa de Carvalho Oliveira
contact affiliation	Université de Sherbrooke
contact email	vanessa.oliveira@usherbrooke.ca
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD078688

PRIDE project URI

• PRIDE
  1. PXD078688
     1. Label: PRIDE project
     2. Name: A feedback loop sustaining neutrophil extracellular trap formation involves S100 proteins, histones, TLR2 and RAGE, and is restrained by albumin