ArticlePloS one2013
Global substrate profiling of proteases in human neutrophil extracellular traps reveals consensus motif predominantly contributed by elastase.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.
- In vitro induction of NETosis: Comprehensive live imaging comparison and systematic review.PloS one · 2017Pooled it
- A proteomic analysis of NETosis in trauma: Emergence of serpinB1 as a key player.The journal of trauma and acute care surgery · 2023Trial
- Role of post-translational modifications in modulating histone reactivity in the extracellular environment.Biochemical Society transactions · 2026Review
- A protease-sensing circuit links neutrophil inflammation to virulence regulation inbioRxiv : the preprint server for biology · 2026Article
- Review
- The Challenges of Detecting Neutrophil CFTR.Journal of innate immunity · 2026Review
- Epicutaneous Staphylococcus aureus initiates cross-tissue IL-36R signaling for neutrophilic lung inflammation in a model of the atopic march.Cell reports · 2025Article
- Exploring the involvement of serine proteases in neutrophil extracellular traps: a review of mechanisms and implications.Cell death & disease · 2025Review
- Assessment of lncRNA biomarkers based on NETs for prognosis and therapeutic response in ovarian cancer.Scientific reports · 2025Article
- Where there's smoke, there's fire: insights from murine models on the effect of cigarette smoke in rheumatoid arthritis development.Frontiers in immunology · 2025Review
- Neutrophil extracellular traps and cannabinoids: potential in cancer metastasis.Frontiers in oncology · 2025Review
- Oxidative stress, DAMPs, and immune cells in acute pancreatitis: molecular mechanisms and therapeutic prospects.Frontiers in immunology · 2025Review
- Conserved specificity of extracellular wastewater peptidases revealed by multiplex substrate profiling by mass spectrometry.Environmental chemistry letters · 2025Article
- From pancreas to lungs: The role of immune cells in severe acute pancreatitis and acute lung injury.Immunity, inflammation and disease · 2024Review
- Composition and Function of Neutrophil Extracellular Traps.Biomolecules · 2024Review
- The In Vitro Effects of Carprofen on Lipopolysaccharide-Induced Neutrophil Extracellular Trap Formation in Dairy Cows.Animals : an open access journal from MDPI · 2024Article
- Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages.Biomedicines · 2024Article
- A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury.International journal of molecular sciences · 2024Review
- Circulating neutrophil extracellular trap remnants as a biomarker to predict outcomes in lupus nephritis.Lupus science & medicine · 2024Article
- A GMR enzymatic assay for quantifying nuclease and peptidase activity.Frontiers in bioengineering and biotechnology · 2024Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Neutrophil extracellular traps (NETs) consist of antimicrobial molecules embedded in a web of extracellular DNA. Formation of NETs is considered to be a defense mechanism utilized by neutrophils to ensnare and kill invading pathogens, and has been recently termed NETosis. Neutrophils can be stimulated to undergo NETosis ex vivo, and are predicted to contain high levels of serine proteases, such as neutrophil elastase (NE), cathepsin G (CG) and proteinase 3 (PR3). Serine proteases are important effectors of neutrophil-mediated immunity, which function directly by degrading pathogenic virulent factors and indirectly via proteolytic activation or deactivation of cytokines, chemokines and receptors. In this study, we utilized a diverse and unbiased peptide library to detect and profile protease activity associated with NETs induced by phorbol-12-myristate-13-acetate (PMA). We obtained a "proteolytic signature" from NETs derived from healthy donor neutrophils and used proteomics to assist in the identification of the source of this proteolytic activity. In addition, we profiled each neutrophil serine protease and included the newly identified enzyme, neutrophil serine protease 4 (NSP4). Each enzyme had overlapping yet distinct endopeptidase activities and often cleaved at unique sites within the same peptide substrate. The dominant proteolytic activity in NETs was attributed to NE; however, cleavage sites corresponding to CG and PR3 activity were evident. When NE was immunodepleted, the remaining activity was attributed to CG and to a lesser extent PR3 and NSP4. Our results suggest that blocking NE activity would abrogate the major protease activity associated with NETs. In addition, the newly identified substrate specificity signatures will guide the design of more specific probes and inhibitors that target NET-associated proteases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.