Evidence map›Paper›PMID 31652502›Full record

ArticleInternational journal of molecular sciences2019

Neutrophil-Derived Microvesicle Induced Dysfunction of Brain Microvascular Endothelial Cells In Vitro.

Anjana Ajikumar, Merete B Long, Paul R Heath, Stephen B Wharton, Paul G Ince, Victoria C Ridger, Julie E Simpson

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

38 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Macropinocytosis as a potential mechanism driving neurotropism ofFrontiers in cellular and infection microbiology · 2023
    Review
  17. Review
  18. Article
  19. Review
  20. Review
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.

Anjana AjikumarSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK. AAjikumar1@sheffield.ac.uk.
Merete B LongDepartment of Infection Immunity and Cardiovascular Diseases, University of Sheffield, Medical School, Sheffield S10 2RX, UK. mlong3@sheffield.ac.uk.
Paul R HeathSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK. p.heath@sheffield.ac.uk.ORCID 0000-0002-8385-1438
Stephen B WhartonSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK. s.wharton@sheffield.ac.uk.
Paul G InceSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK. p.g.ince@sheffield.ac.uk.
Victoria C RidgerDepartment of Infection Immunity and Cardiovascular Diseases, University of Sheffield, Medical School, Sheffield S10 2RX, UK. v.c.ridger@sheffield.ac.uk.
Julie E SimpsonSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK. julie.simpson@sheffield.ac.uk.ORCID 0000-0002-3753-4271
University of Sheffield · GB

Funding

Alzheimer's Research UK ARUK-PhD2016-5Medical Research Council G0300126Medical Research Council G0900582Medical Research Council G9901400Medical Research Council MR/J004308/1
6 · The paper itself

Abstract

The blood-brain barrier (BBB), composed of brain microvascular endothelial cells (BMEC) that are tightly linked by tight junction (TJ) proteins, restricts the movement of molecules between the periphery and the central nervous system. Elevated systemic levels of neutrophils have been detected in patients with altered BBB function, but the role of neutrophils in BMEC dysfunction is unknown. Neutrophils are key players of the immune response and, when activated, produce neutrophil-derived microvesicles (NMV). NMV have been shown to impact the integrity of endothelial cells throughout the body and we hypothesize that NMV released from circulating neutrophils interact with BMEC and induce endothelial cell dysfunction. Therefore, the current study investigated the interaction of NMV with human BMEC and determined whether they altered gene expression and function in vitro. Using flow cytometry and confocal imaging, NMV were shown to be internalized by the human cerebral microvascular endothelial cell line hCMEC/D3 via a variety of energy-dependent mechanisms, including endocytosis and macropinocytosis. The internalization of NMV significantly altered the transcriptomic profile of hCMEC/D3, specifically inducing the dysregulation of genes associated with TJ, ubiquitin-mediated proteolysis and vesicular transport. Functional studies confirmed NMV significantly increased permeability and decreased the transendothelial electrical resistance (TEER) of a confluent monolayer of hCMEC/D3. These findings indicate that NMV interact with and affect gene expression of BMEC as well as impacting their integrity. We conclude that NMV may play an important role in modulating the permeability of BBB during an infection.

Indexed as

Blood-Brain BarrierCapillary PermeabilityCells, CulturedEndocytosisEndothelial CellsEndothelium, VascularExtracellular VesiclesHumansNeutrophilsblood brain barrierendothelial cellsgene expressionmicrovesiclesneutrophilspermeabilityTEER

Identifiers

PMID31652502
PMCPMC6834153
OpenAlexW2980736644

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.