ArticleProceedings of the National Academy of Sciences of the United States of America2012
NSP4, an elastase-related protease in human neutrophils with arginine specificity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 108 citations in OpenAlex.
- Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Recent Advances in Fluorescent Probes for Imaging Enzyme Activity in NETosis.Chembiochem : a European journal of chemical biology · 2026Review
- Embryonic Phase Transition/Separation on Hepatic Liquid Crystal Droplets Is Essential for Liver Development.Biology · 2026Article
- Exploring the involvement of serine proteases in neutrophil extracellular traps: a review of mechanisms and implications.Cell death & disease · 2025Review
- Age-Associated Proteomic Changes in Human Spermatozoa.International journal of molecular sciences · 2025Article
- Enhanced Porcine Reproductive and Respiratory Syndrome Virus Replication in Nsp4- or Nsp2-Overexpressed Marc-145 Cell Lines.Veterinary sciences · 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
- Innate Immune Mechanisms in Normal and Adverse Pregnancy.Advances in experimental medicine and biology · 2025Review
- Versatile roles for neutrophil proteinase 3 in hematopoiesis and inflammation.Immunologic research · 2024Review
- Cathepsin C in health and disease: from structural insights to therapeutic prospects.Journal of translational medicine · 2024Review
- Article
- Human Neutrophil Elastase: Characterization of Intra- vs. Extracellular Inhibition.International journal of molecular sciences · 2024Article
- CRISPR-Cas9n-mediated ELANE promoter editing for gene therapy of severe congenital neutropenia.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- Targeted Library of Phosphonic-Type Inhibitors of Human Neutrophil Elastase.Molecules (Basel, Switzerland) · 2024Article
- Biosensing Platform for the Detection of Biomarkers for ALI/ARDS in Bronchoalveolar Lavage Fluid of LPS Mice Model.Biosensors · 2023Article
- Article
- Cysteine Cathepsins as Therapeutic Targets in Immune Regulation and Immune Disorders.Biomedicines · 2023Review
- Effect of Deposition and Protease Digestion on the Ex Vivo Activity of Antimicrobial Peptide-Coated Contact Lenses.Nanomaterials (Basel, Switzerland) · 2023Article
- Origin and Expansion of the Serine Protease Repertoire in the Myelomonocyte Lineage.International journal of molecular sciences · 2021Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophil serine proteases (NSPs) in cytoplasmic granules of neutrophils are regarded as important antimicrobial defense weapons after engulfment and exposure of pathogens to the content of primary granules. Despite intensive studies on neutrophils during the last three decades, only three active serine proteases, neutrophil elastase (NE), cathepsin G (CG), and proteinase 3 (PR3) have been identified in these short-lived cells. Here, we report on the identification of a fourth serine protease (NSP4) with 39% identity to NE and PR3, but arginine specificity, yet sharing features like propeptide processing by dipeptidyl peptidase I, storage, and release as an active enzyme with the three active proteases. We established monoclonal antibodies against NSP4, excluded cross-reactivity to human granzymes, NE, CG, PR3, and azurocidin, and screened for NSP4 protein expression in various human tissues and blood leukocyte populations. Only granulocyte precursors and neutrophil populations from peripheral blood were positive. The content of NSP4 in neutrophil lysates, however, was about 20-fold lower compared with CG. Upon neutrophil activation, NSP4 was released into the supernatant. Profiling its specificity with peptide libraries from Escherichia coli revealed a preference for arginine in P1; it cleaved Tyr-Arg-Phe-Arg-AMC and Ala-Pro-Nva-thiobenzyl esters. NSP4 was inhibited by α(1)-proteinase inhibitor (α(1)-antitrypsin), C1 inhibitor, and most efficiently by antithrombin-heparin, but not by elafin, secretory leukocyte protease inhibitor, α(1)-antichymotrypsin, and monocyte-neutrophil elastase inhibitor. Functional specialization and preferred natural substrates of NSP4 remain to be determined to understand the biological interplay of all four NSPs during neutrophil responses.
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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.