ArticleKidney international2015
Neutrophil serine proteases exert proteolytic activity on endothelial cells.
Article in Kidney international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- The relationship of neutrophil elastase and proteinase 3 with risk factors, and chronic complications in type 2 diabetes: A Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) sub-study.Diabetes & vascular disease researchTrial
- Neutrophil serine proteases degrade endothelial cortactin and promote extravasation.The Journal of cell biology · 2026Article
- Intramuscular neutrophil-derived immunometabolic niches locally boost insulin-responsive GLUT4 translocation after muscle contraction.The Journal of physiology · 2026Article
- Dysregulated iron metabolism associates with neutrophilic airway inflammation in COPD.Clinical science (London, England : 1979) · 2026Article
- Role of neutrophils in regulating vascular permeability in inflammatory and autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Effect of mosquito saliva from distinct species on human dermal endothelial cell functionEmerging microbes & infections · 2025Article
- Comprehensive Analysis of RNA Methylation-Regulated Gene Signature and Immune Infiltration in Ischemia/Reperfusion-Induced Acute Kidney Injury.Kidney & blood pressure research · 2025Article
- The Roles of Oxidative Stress and Red Blood Cells in the Pathology of the Varicose Vein.International journal of molecular sciences · 2024Review
- The Proteolytic Activity of Neutrophil-Derived Serine Proteases Bound to the Cell Surface Arming Lung Epithelial Cells for Viral Defense.Molecules (Basel, Switzerland) · 2024Article
- Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Quantitative Proteomic Characterization of Foreign Body Response towards Silicone Breast Implants Identifies Chronological Disease-Relevant Biomarker Dynamics.Biomolecules · 2023Article
- Dipeptidyl peptidase 1 inhibition as a potential therapeutic approach in neutrophil-mediated inflammatory disease.Frontiers in immunology · 2023Review
- Protective α1-antitrypsin effects in autoimmune vasculitis are compromised by methionine oxidation.The Journal of clinical investigation · 2022Article
- Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis.Biomedicines · 2022Review
- Selective decrease in alpha1-antitrypsin levels in diabetic retinopathy: Could the levels of it be playing a role in the pathophysiology of diabetic retinopathy?The Indian journal of medical research · 2022Article
- Proteinase 3 contributes to endothelial dysfunction in an experimental model of sepsis.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Neutrophil-Derived Proteases Contribute to the Pathogenesis of Early Diabetic Retinopathy.Investigative ophthalmology & visual science · 2021Article
- Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia.Redox biology · 2021Review
- Neutrophil Gelatinase-Associated Lipocalin Protects from ANCA-Induced GN by Inhibiting TJournal of the American Society of Nephrology : JASN · 2020Article
- Evolution of multifunctionality through a pleiotropic substitution in the innate immune protein S100A9.eLife · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophil serine proteases (NSPs) are released from activated neutrophils during inflammation. Here we studied the transfer of the three major NSPs, namely proteinase 3, human neutrophil elastase, and cathepsin G, from neutrophils to endothelial cells and used an unbiased approach to identify novel endothelial NSP substrates. Enzymatically active NSPs were released from stimulated neutrophils and internalized by endothelial cells in a dose- and time-dependent manner as shown by immunoblotting, flow cytometry, and the Boc-Ala substrate assay. Using terminal-amine isotopic labeling of substrates in endothelial cells, we identified 121 peptides from 82 different proteins consisting of 36 substrates for proteinase 3, 30 for neutrophil elastase, and 28 for cathepsin G, respectively. We characterized the extended cleavage pattern and provide corresponding IceLogos. Gene ontology analysis showed significant cytoskeletal substrate enrichment and confirmed several cytoskeletal protein substrates by immunoblotting. Finally, ANCA-stimulated neutrophils released all three active NSPs into the supernatant. Supernatants increased endothelial albumin flux and disturbed the endothelial cell cytoskeletal architecture. Serine protease inhibition abrogated this effect. Longer exposure to NSPs reduced endothelial cell viability and increased apoptosis. Thus, we identified novel NSP substrates and suggest NSP inhibition as a therapeutic measure to inhibit neutrophil-mediated inflammatory vascular diseases.
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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.