PXD057968

PXD057968 is an original dataset announced via ProteomeXchange.

Title	Investigating Neutrophil Responses to Stimuli: Comparative Analysis of reactive species- dependent and independent mechanisms
Description	Neutrophils play a critical role in immune response, using mechanisms as degranulation, and release of neutrophil extracellular traps (NETs) to combat pathogens. NETs are web-like structures composed of chromatin and microbicidal proteins, released by neutrophils in response to many different stimuli. Recent evidences suggest multiple mechanisms might be involved in neutrophil’s response to stimuli, but the biochemical characterization of each different pathway is still lacking. In this study, we used superoxide measurements, live-imaging microscopy and high-resolution proteomics to provide a careful biochemical characterization of the neutrophil’s response following activation by two commonly used, well characterized stimuli, namely phorbol-12-myristate-13-acetate (PMA) , and ionomycin, a calcium ionophore. Our results demonstrated that although both stimuli induce extracellular DNA release, signals and mediators released by activated cells before this final event were distinct. Thus, PMA-treated neutrophils induce superoxide production, and degranulation of proteins from all granules, especially those derived from secretory vesicles and tertiary granules. On the other hand, ionomycin-treated neutrophils do not stimulate superoxide generation, but induce extensive protein citrullination particularly in the proteins related to actin cytoskeleton organization, nucleus stability, and the NADPH oxidase complex. Interestingly, many of the citrullinated proteins detected in this work were also found to act as autoantigens in autoimmune diseases such as rheumatoid arthritis. These striking differences show neutrophils’ response to PMA and ionomycin are two distinct biochemical processes that might exemplify distinct response to the environment. It also provides implications for understanding neutrophil-driven microbial response and potential roles in autoimmune diseases.
HostingRepository	PRIDE
AnnounceDate	2025-03-03
AnnouncementXML	Submission_2025-03-03_05:28:38.100.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rafaela Nascimento
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-17 11:25:52	ID requested
⏵ 1	2025-03-03 05:28:38	announced

10.1016/J.REDOX.2025.103540;

submitter keyword: degranulation,Neutrophil extracellular traps, ionomycin, NADPH oxidase activation, PMA

Graziella Eliza Ronsein
contact affiliation	Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil
contact email	ronsein@iq.usp.br
lab head
Rafaela Nascimento
contact affiliation	University of São Paulo - Department of Biochemistry
contact email	rnascimento@iq.usp.br
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057968
     1. Label: PRIDE project
     2. Name: Investigating Neutrophil Responses to Stimuli: Comparative Analysis of reactive species- dependent and independent mechanisms