Dataset Information

CONNETTING ANTI-2GLYCOPROTEIN I ANTIBODIES, NETosis AND ENDOTHELIAL CELL ACTIVATION

ABSTRACT: This project aims to explore the intricate relationship between anti-β2glycoprotein I (aβ2GPI) antibodies, neutrophil extracellular traps (NETs), and endothelial cell activation in Antiphospholipid Syndrome (APS), an autoimmune disorder characterized by thrombotic events. This study tested the hypothesis that aβ2GPI antibodies may both induce NETosis and act as NET-binding antibodies. It further evaluated the ability of aβ2GPI-induced NET to cause endothelial activation, TF expression increase and endothelial disfunction. Furthermore, a proteomics analysis was conducted to compare aβ2GPI-induced NETs with NETs induced by phorbol myristate acetate (PMA). Please note that aβ2GPI-induced NETs are labeled as 'TV' in the raw files, while PMA-induced NETs are labeled as 'T'.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Neutrophil

SUBMITTER: Martina Bartolucci

LAB HEAD: Andrea Petretto

PROVIDER: PXD052010 | Pride | 2025-08-25

REPOSITORIES: Pride

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Publications

Anti-β2glycoprotein I-induced neutrophil extracellular traps cause endothelial activation.

Mancuso Silvia S Caliste Mattia M Petretto Andrea A Corsiero Elisa E Grinovero Nicole N Capozzi Antonella A Riitano Gloria G Barbati Cristiana C Truglia Simona S Alessandri Cristiano C Sorice Maurizio M Bombardieri Michele M Conti Fabrizio F

Rheumatology (Oxford, England) 20250801 8

<h4>Objective</h4>Neutrophil extracellular traps (NETs) involvement in antiphospholipid syndrome (APS) pathogenesis is known, but the role of anti-β2glycoprotein I (aβ2GPI) antibodies-induced NETs in triggering a procoagulant and proinflammatory phenotype in endothelial cells (ECs) remains to be evaluated. This study investigated whether NET-aβ2GPI can activate ECs and whether NET-aβ2GPI and NET-phorbol myristate acetate (PMA) have different proteomic profiles.<h4>Methods</h4>Healthy donor (HD) ...[more]

PMID: 40238197

Similar Datasets

Project description:Extracellular traps (NETs) are released by neutrophils during inflammation and play a role in pathology of diseases such as atherosclerosis, as well as their innate immune function of clearing infection. NETs are composed of a mesh of DNA and histones and contain various anti-microbial granule proteins, such as myeloperoxidase (MPO), which remains enzymatically active. This can result in the production of the reactive oxidant hypochlorous acid (HOCl), which reacts readily with proteins. However, whether histones and other NET-associated proteins contain HOCl-modified proteins is unknown. This is significant as recent studies show that exposure of histones to HOCl alters their extracellular reactivity to promote inflammatory signaling in vascular cells. In this study, we used a proteomic approach to characterise the protein composition of NETs and examine whether histones and other proteins contain oxidative protein-translational modifications resulting from reactions with HOCl. NETs were collected from neutrophil-like PLB-985 cells and primary neutrophils stimulated with phorbol myristate acetate (PMA) or nigericin, a bacterial peptide derived from Streptomyces hygroscopicus. Exposure of proteins to HOCl results in the formation of nitrile and aminoadipic semialdehyde formation on lysine residues, chlorination of tyrosine and tryptophan residues together with methionine oxidation products. Evidence was obtained for the presence of tyrosine chlorination on histones, particularly histone H4, and other proteins like quinone oxidoreductase. Other PTMs, including citrullination and acetylation were also detected on histones (H1, H2A, H3 and H4). Chlorination of the histone H4 peptide TVTAMDVVYALK(R) by HOCl was more abundant in NETs obtained from neutrophils exposed to PMA compared to nigericin, consistent with nigericin triggering NET release via a non-oxidative pathway. Current studies are investigating whether histone modifications occur before or after release from the cell. These findings provide the first evidence that HOCl induces histone modifications on NETs, which may be relevant in disease.

			Action	DRS
	Conti_NET_T1_20.raw	Raw
	Conti_NET_T2_21.raw	Raw
	Conti_NET_T3_22.raw	Raw
	Conti_NET_T4_23.raw	Raw
	Conti_NET_T5_24.raw	Raw