ArticleBiomaterials2020
Inhibition of neutrophil elastase prevents neutrophil extracellular trap formation and rescues mice from endotoxic shock.
Article in Biomaterials, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 182 citations in OpenAlex.
- Interfacial mild alkalinity shapes Neutrophil immunometabolism through sphingolipid remodeling to enhance antibacterial host defense.Materials today. Bio · 2026Article
- The C5a-C5aR1 axis facilitates blood-brain barrier disruption induced by EV-A71 infection through neutrophil activation.PLoS pathogens · 2026Article
- Neutrophil-targeted nanoparticles delivering sivelestat alleviate cerebral ischemia-reperfusion injury by suppressing NETosis.Materials today. Bio · 2026Article
- Neutrophil extracellular traps drive cholangiocyte injury via ZNF709-TP53-MDM2 pathway in primary biliary cholangitis.Hepatology international · 2026Article
- A 'Tangled Web' in the CNS: unraveling neutrophil extracellular traps in neurological disorders.Molecular neurodegeneration · 2026Review
- Spatiotemporal heterogeneity of neutrophil extracellular traps in hepatocellular carcinoma microenvironment and targeted therapy progress.Journal of translational medicine · 2026Review
- Neutrophils and neutrophil extracellular traps in diabetes mellitus and its complications: Mechanisms and therapeutic implications.iScience · 2026Review
- Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review).International journal of molecular medicine · 2026Review
- NETosis mediates tick blood pool formation.The Journal of veterinary medical science · 2026Article
- SodA promotes immune evasion ofMicrobiology spectrum · 2026Article
- The use of sivelestat sodium among patients with acute pancreatitis and early organ failure: a single-center retrospective cohort study.Frontiers in medicine · 2026Article
- Differential Regulation of Granule Release in Platelets and Immune Cells.TH open : companion journal to thrombosis and haemostasis · 2026Article
- Mapping benefit, risk, and opportunity in PAD4 inhibition.Frontiers in immunology · 2026Review
- Neutrophil Extracellular Traps in Diabetic Kidney Disease: Mechanisms of Pathogenesis and Emerging Therapeutic Strategies.Drug design, development and therapy · 2026Review
- Neutrophil in sepsis: functional aberration and regulated cell death.Frontiers in immunology · 2026Review
- Advances in Targeting Neutrophil Extracellular Traps as a Promising Approach for Breast Cancer Treatment.Combinatorial chemistry & high throughput screening · 2026Review
- Neutrophil extracellular traps in diabetic wound healing: mechanisms, pathological roles, and therapeutic implications.Burns & trauma · 2026Review
- Research progress on neutrophil extracellular traps and hepatitis-to-hepatocellular carcinoma transformation (Review).Oncology letters · 2026Review
- Mechanistic interplay between extracellular vesicles and neutrophil extracellular traps: unveiling the "sterile inflammation" cascade in obesity-induced diabetes progression.Frontiers in immunology · 2026Review
- Inhibiting the formation of neutrophil extracellular traps to prevent the recurrence of post-operative glioblastoma.Nature communications · 2025Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Neutrophil elastase (NE) is a serine protease stored in the azurophilic granules of neutrophils and released into the extracellular milieu during inflammatory response or formation of neutrophil extracellular traps (NETs). Neutrophils release NETs to entrap pathogens by externalizing their cellular contents in a DNA framework decorated with anti-microbials and proteases, including NE. Importantly, excess NETs in tissues are implicated in numerous pathologies, including sepsis, rheumatoid arthritis, vasculitis, and cancer. However, it remains unknown how to effectively prevent NET formation. Here, we show that NE plays a major role during NET formation and that inhibition of NE is a promising approach for decreasing NET-mediated tissue injury. NE promoted NET formation by human neutrophils. Whereas sivelestat, a small molecule inhibitor of NE, inhibited the formation of NETs in vitro , administration of free sivelestat did not have any efficacy in a murine model of lipopolysaccharide-induced endotoxic shock. To improve the efficacy of sivelestat in vivo, we have developed a nanoparticle system for delivering sivelestat. We demonstrate that nanoparticle-mediated delivery of sivelestat effectively inhibited NET formation, decreased the clinical signs of lung injury, reduced NE and other proinflammatory cytokines in serum, and rescued animals against endotoxic shock. Collectively, our data demonstrates that NE signaling can initiate NET formation and that nanoparticle-mediated inhibition of NE improves drug efficacy for preventing 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.