Evidence map›Paper›PMID 29556228›Full record

ArticleFrontiers in immunology2018

Development and Application of High-Content Biological Screening for Modulators of NET Production.

Ilaria J Chicca, Michael R Milward, Iain Leslie C Chapple, Gareth Griffiths, Rod Benson, Thomas Dietrich, Paul R Cooper

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 21% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
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

7 authors at 1 institution in 1 country.

Ilaria J ChiccaSchool of Dentistry, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom.
Michael R MilwardSchool of Dentistry, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom.
Iain Leslie C ChappleSchool of Dentistry, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom.
Gareth GriffithsImagen Therapeutics Ltd., Manchester, United Kingdom.
Rod BensonImagen Therapeutics Ltd., Manchester, United Kingdom.
Thomas DietrichSchool of Dentistry, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom.
Paul R CooperSchool of Dentistry, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom.
University of Birmingham · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neutrophil extracellular traps (NETs) are DNA-based antimicrobial web-like structures whose release is predominantly mediated by reactive oxygen species (ROS); their purpose is to combat infections. However, unbalanced NET production and clearance is involved in tissue injury, circulation of auto-antibodies and development of several chronic diseases. Currently, there is lack of agreement regarding the high-throughput methods available for NET investigation. This study, therefore, aimed to develop and optimize a high-content analysis (HCA) approach, which can be applied for the assay of NET production and for the screening of compounds involved in the modulation of NET release. A suitable paraformaldehyde fixation protocol was established to enable HCA of neutrophils and NETs. Bespoke and in-built bioinformatics algorithms were validated by comparison with standard low-throughput approaches for application in HCA of NETs. Subsequently, the optimized protocol was applied to high-content screening (HCS) of a pharmaceutically derived compound library to identify modulators of NETosis. Of 56 compounds assessed, 8 were identified from HCS for further characterization of their effects on NET formation as being either inducers, inhibitors or biphasic modulators. The effects of these compounds on naïve neutrophils were evaluated by using specific assays for the induction of ROS and NET production, while their modulatory activity was validated in phorbol 12-myristate 13-acetate-stimulated neutrophils. Results indicated the involvement of glutathione reductase, Src family kinases, molecular-target-of-Rapamycin, and mitogen-activated-protein-kinase pathways in NET release. The compounds and pathways identified may provide targets for novel therapeutic approaches for treating NET-associated pathologies.

Indexed as

Pharmaceutical PreparationsExtracellular TrapsFemaleHumansMaleMAP Kinase Signaling SystemNeutrophilsReactive Oxygen Speciessrc-Family KinasesPharmaceutical PreparationsReactive Oxygen Speciessrc-Family Kinasesglutathione reductasehigh-content analysishigh-content screeningMAPKmTORneutrophil extracellular trapsnuclear decondensationSrc

Identifiers

PMID29556228
PMCPMC5844942
OpenAlexW2789121171

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.