Evidence map›Paper›PMID 27599294›Full record

ArticleThe Journal of clinical investigation2016

Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation.

Christian C Yost, Hansjörg Schwertz, Mark J Cody, Jared A Wallace, Robert A Campbell, Adriana Vieira-de-Abreu, Claudia V Araujo, Sebastian Schubert, Estelle S Harris, Jesse W Rowley and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

103 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Observational
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 3 countries.

Christian C Yost
Hansjörg Schwertz
Mark J Cody
Jared A Wallace
Robert A Campbell
Adriana Vieira-de-Abreu
Claudia V Araujo
Sebastian Schubert
Estelle S Harris
Jesse W Rowley
Matthew T Rondina
James M Fulcher
Curry L Koening
Andrew S Weyrich
Guy A Zimmerman
University of Utah · USInstitute of Molecular Medicine · IN

Funding

Translational Research Skills Development CoreU54HL112311 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S, ZIMMERMAN, GUY A. · 2012 to 2016
$12.9M
TRANSLATIONAL EVENTS IN PLATELETSR01HL066277 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S · 2001 to 2012
$3.8M
Molecular Interactions of Myeloid Cells with EndotheliumR37HL044525 · NHLBI · UNIVERSITY OF UTAH · PI ZIMMERMAN, GUY A. · 2004 to 2013
$3.5M
The Effects of ART on Platelets and HIV-Associated ThrombosisR01HL126547 · NHLBI · UNIVERSITY OF UTAH · PI PLANELLES, VICENTE, RONDINA, MATTHEW THOMAS · 2014 to 2017
$3.0M
Platelet Immune Responses in Aging and InfluenzaR01AG048022 · NIA · UNIVERSITY OF UTAH · PI RONDINA, MATTHEW THOMAS · 2014 to 2018
$1.8M
The Platelet Metabolome in ObesityK01GM103806 · NIGMS · UNIVERSITY OF UTAH · PI ROWLEY, JESSE · 2012 to 2016
$802k
Translational Regulation of Gene Expression in Neonatal PMNsK08HD049699 · NICHD · UNIVERSITY OF UTAH · PI YOST, CHRISTIAN CON · 2006 to 2010
$673k
The Regulation of Inflammatory Gene Responses in AgingR03AG040631 · NIA · UNIVERSITY OF UTAH · PI RONDINA, MATTHEW THOMAS · 2011 to 2012
$149k
NHLBI NIH HHS R01 HL066277NHLBI NIH HHS R01 HL126547NHLBI NIH HHS R37 HL044525NHLBI NIH HHS U54 HL112311NIA NIH HHS R01 AG048022NIA NIH HHS R03 AG040631NICHD NIH HHS K08 HD049699NIGMS NIH HHS K01 GM103806
6 · The paper itself

Abstract

Neutrophil granulocytes, also called polymorphonuclear leukocytes (PMNs), extrude molecular lattices of decondensed chromatin studded with histones, granule enzymes, and antimicrobial peptides that are referred to as neutrophil extracellular traps (NETs). NETs capture and contain bacteria, viruses, and other pathogens. Nevertheless, experimental evidence indicates that NETs also cause inflammatory vascular and tissue damage, suggesting that identifying pathways that inhibit NET formation may have therapeutic implications. Here, we determined that neonatal NET-inhibitory factor (nNIF) is an inhibitor of NET formation in umbilical cord blood. In human neonatal and adult neutrophils, nNIF inhibits key terminal events in NET formation, including peptidyl arginine deiminase 4 (PAD4) activity, neutrophil nuclear histone citrullination, and nuclear decondensation. We also identified additional nNIF-related peptides (NRPs) that inhibit NET formation. nNIFs and NRPs blocked NET formation induced by pathogens, microbial toxins, and pharmacologic agonists in vitro and in mouse models of infection and systemic inflammation, and they improved mortality in murine models of systemic inflammation, which are associated with NET-induced collateral tissue injury. The identification of NRPs as neutrophil modulators that selectively interrupt NET generation at critical steps suggests their potential as therapeutic agents. Furthermore, our results indicate that nNIF may be an important regulator of NET formation in fetal and neonatal inflammation.

Indexed as

AnimalsBlood ProteinsCells, CulturedChromatin Assembly and DisassemblyExtracellular TrapsFetal BloodHistonesHumansInfant, NewbornInflammationLipopolysaccharidesMaleMice, Inbred C57BLNeoplasm ProteinsNeutrophilsProtein Processing, Post-TranslationalBlood Proteinscancer-recognition, immunedefense suppression, serine protease protection peptideHistonesLipopolysaccharidesNeoplasm ProteinsnNIF peptide, human

Identifiers

PMID27599294
PMCPMC5096809
OpenAlexW2510402218

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.