ArticleFrontiers in immunology2019
Citrullination Licenses Calpain to Decondense Nuclei in Neutrophil Extracellular Trap Formation.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Review
- Chromatin decompaction within the nucleus increases plasma membrane tension promoting NETosis execution, independently of transcription.Nature communications · 2026Article
- Recent Advances in Fluorescent Probes for Imaging Enzyme Activity in NETosis.Chembiochem : a European journal of chemical biology · 2026Review
- Research progress on neutrophil extracellular traps in sepsis‑induced coagulopathy (Review).Molecular medicine reports · 2026Review
- Neutrophil extracellular traps (NETosis) in gynecologic cancers: from pathogenesis to therapeutic opportunities: a narrative review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Roles of neutrophil extracellular traps in cancer immunotherapy resistance and therapeutic targeting.Biomarker research · 2026Review
- The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis of Ovarian Cancer: New Insight and Future Perspectives.Molecular biotechnology · 2026Review
- Neutrophil Extracellular Traps in Cancer Metastasis: From Mechanistic Understanding to Targeted Therapy.Current oncology (Toronto, Ont.) · 2026Review
- A feedback loop sustaining neutrophil extracellular trap formation involves S100 proteins, histones, TLR2 and RAGE, and is restrained by albumin.Frontiers in immunology · 2026Article
- Interactions between neutrophil extracellular traps and macrophages: the key to inflammatory diseases.Frontiers in immunology · 2026Review
- The hormone-microbiota-NET framework in gynecologic diseases: evidence, controversies, and translational opportunities.Frontiers in immunology · 2026Review
- NETs in ovarian cancer progression: innovative nanoparticle-based therapeutic strategies.European journal of medical research · 2025Review
- Review
- Anti-IBD activity of Eleusine indica through inhibition of TNF-alpha and p38 MAPK expression.Inflammopharmacology · 2025Article
- Exploring neutrophil extracellular traps: mechanisms of immune regulation and future therapeutic potential.Experimental hematology & oncology · 2025Review
- [Research Progress of Neutrophil Extracellular Traps in Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- The emerging role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases.MedComm · 2025Review
- Blocking peptidyl arginine deiminase 4 confers neuroprotective effect in the post-ischemic brain through both NETosis-dependent and -independent mechanisms.Acta neuropathologica communications · 2025Article
- Sepsis-induced NET formation requires MYD88 but is independent of GSDMD and PAD4.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophils respond to various stimuli by decondensing and releasing nuclear chromatin characterized by citrullinated histones as neutrophil extracellular traps (NETs). This achieves pathogen immobilization or initiation of thrombosis, yet the molecular mechanisms of NET formation remain elusive. Peptidyl arginine deiminase-4 (PAD4) achieves protein citrullination and has been intricately linked to NET formation. Here we show that citrullination represents a major regulator of proteolysis in the course of NET formation. Elevated cytosolic calcium levels trigger both peptidylarginine deiminase-4 (PAD4) and calpain activity in neutrophils resulting in nuclear decondensation typical of NETs. Interestingly, PAD4 relies on proteolysis by calpain to achieve efficient nuclear lamina breakdown and chromatin decondensation. Pharmacological or genetic inhibition of PAD4 and calpain strongly inhibit chromatin decondensation of human and murine neutrophils in response to calcium ionophores as well as the proteolysis of nuclear proteins like lamin B1 and high mobility group box protein 1 (HMGB1). Taken together, the concerted action of PAD4 and calpain induces nuclear decondensation in the course of calcium-mediated NET formation.
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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.