ArticleBlood2015
PAD4-deficiency does not affect bacteremia in polymicrobial sepsis and ameliorates endotoxemic shock.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 3 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
141 citing papers in PubMed, 3 syntheses or guidelines pooled it, 221 citations in OpenAlex.
- A consensus blood transcriptomic framework for sepsis.Nature medicine · 2025Guideline
- Investigating the Role of Neutrophil Extracellular Traps as a Therapeutic Target in Traumatic Brain Injury: a Systematic Review and Meta-analysis.Molecular neurobiology · 2025Pooled it
- Characteristics and Role of Neutrophil Extracellular Traps in Asthma.Inflammation · 2022Pooled it
- Epigenetic regulation of neutrophil dysfunction in sepsis: mechanisms, biomarkers, and translational challenges.Journal of translational medicine · 2026Review
- Immunology of Sepsis.Clinics in chest medicine · 2026Review
- Peritoneal neutrophil extracellular traps contribute to septic AKI via peritoneal IL-17A and distant organ CXCL-1/ CXCL-2 pathway in abdominal sepsis.Scientific reports · 2026Article
- The hormone-microbiota-NET framework in gynecologic diseases: evidence, controversies, and translational opportunities.Frontiers in immunology · 2026Review
- Targeting neutrophil extracellular traps in bacterial infections: mechanistic insights and translational perspectives.Frontiers in immunology · 2026Review
- Review
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- Peritoneal Neutrophil Extracellular Traps contribute to septic AKI via peritoneal IL-17A and distant organ CXCL-1/ CXCL-2 pathway in abdominal sepsis.Research square · 2025Article
- CitH3, a Druggable Biomarker for Human Diseases Associated with Acute NETosis and Chronic Immune Dysfunction.Pharmaceutics · 2025Review
- From Circulating Biomarkers to Polymorphic Variants: A Narrative Review of Challenges in Thrombophilia Evaluation.Journal of clinical medicine · 2025Review
- The Role of Extracellular-Vesicle-Derived miRNAs in Postoperative Organ Dysfunction in Neonates and Infants Undergoing Congenital Cardiac Surgery: An Exploratory Study.International journal of molecular sciences · 2025Article
- Circulating NETs enable early identification of thrombotic risk in sepsis at emergency care onset.Frontiers in immunology · 2025Article
- Neutrophil extracellular traps in sepsis: trade-off between pros and cons.Burns & trauma · 2025Review
- Sex-specific effects of peptidyl arginine deiminase 4 deficiency in the cafeteria diet-induced obesity-associated metabolic complications.Frontiers in endocrinology · 2025Article
- Neutrophil Extracellular Traps in Sepsis and Sepsis-Related Organ Dysfunction.ImmunoTargets and therapy · 2025Review
- Loss of PADI2 and PADI4 ameliorates sepsis-induced acute lung injury by suppressing NLRP3+ macrophages.JCI insight · 2024Article
- Inhibitors of Polyphosphate and Neutrophil Extracellular Traps.Seminars in thrombosis and hemostasis · 2024Review
81 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 3 institutions in 1 country.
Funding
Abstract
Neutrophil extracellular traps (NETs), consisting of nuclear DNA with histones and microbicidal proteins, are expelled from activated neutrophils during sepsis. NETs were shown to trap microbes, but they also fuel cardiovascular, thrombotic, and autoimmune disease. The role of NETs in sepsis, particularly the balance between their antimicrobial and cytotoxic actions, remains unclear. Neutrophils from peptidylarginine deiminase 4-(PAD4(-/-)) deficient mice, which lack the enzyme allowing for chromatin decondensation and NET formation, were evaluated. We found that neutrophil functions involved in bacterial killing, other than NETosis, remained intact. Therefore, we hypothesized that prevention of NET formation might not have devastating consequences in sepsis. To test this, we subjected the PAD4(-/-) mice to mild and severe polymicrobial sepsis produced by cecal ligation and puncture. Surprisingly, under septic conditions, PAD4(-/-) mice did not fare worse than wild-type mice and had comparable survival. In the presence of antibiotics, PAD4-deficiency resulted in slightly accelerated mortality but bacteremia was unaffected. PAD4(-/-) mice were partially protected from lipopolysaccharide-induced shock, suggesting that PAD4/NETs may contribute to the toxic inflammatory and procoagulant host response to endotoxin. We propose that preventing NET formation by PAD4 inhibition in inflammatory or thrombotic diseases is not likely to increase host vulnerability to bacterial infections.
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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.