Evidence map›Paper›PMID 24779584›Full record

ArticleAging cell2014

Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals.

Jon Hazeldine, Phillipa Harris, Iain L Chapple, Melissa Grant, Hannah Greenwood, Amy Livesey, Elizabeth Sapey, Janet M Lord

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed, 1 pooled it
8.8field-weighted citation impact, top 2% 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

171 citing papers in PubMed, 1 synthesis or guideline pooled it, 286 citations in OpenAlex.

  1. Pooled it
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  10. What Do We Know About Immune System Aging from Human and Animal Studies?International journal of molecular sciences · 2026
    Review
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  12. hLife · 2026
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  13. Article
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111 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

8 authors at 1 institution in 1 country.

Jon HazeldineMRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, Birmingham University Medical School, Birmingham, B15 2TT, UK.
Phillipa Harris
Iain L Chapple
Melissa Grant
Hannah Greenwood
Amy Livesey
Elizabeth Sapey
Janet M Lord
University of Birmingham · GB

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council 1090321Medical Research Council MR/L008335/1
6 · The paper itself

Abstract

Neutrophil extracellular traps (NETs) are a recently discovered addition to the defensive armamentarium of neutrophils, assisting in the immune response against rapidly dividing bacteria. Although older adults are more susceptible to such infections, no study has examined whether aging in humans influences NET formation. We report that TNF-α-primed neutrophils generate significantly more NETs than unprimed neutrophils and that lipopolysaccharide (LPS)- and interleukin-8 (IL-8)-induced NET formation exhibits a significant age-related decline. NET formation requires generation of reactive oxygen species (ROS), and this was also reduced in neutrophils from older donors identifying a mechanism for reduced NET formation. Expression of IL-8 receptors (CXCR1 and CXCR2) and the LPS receptor TLR4 was similar on neutrophils from young and old subjects, and neutrophils challenged with phorbol-12-myristate-13-acetate (PMA) showed no age-associated differences in ROS or NET production. Taken together, these data suggest a defect in proximal signalling underlies the age-related decline in NET and ROS generation. TNF-α priming involves signalling through p38 MAP kinase, but activation kinetics were comparable in neutrophils from young and old donors. In a clinical setting, we assessed the capacity of neutrophils from young and older patients with chronic periodontitis to generate NETs in response to PMA and hypochlorous acid (HOCL). Neutrophil extracellular trap generation to HOCL, but not PMA, was lower in older periodontitis patients but not in comparison with age-matched controls. Impaired NET formation is thus a novel defect of innate immunity in older adults but does not appear to contribute to the increased incidence of periodontitis in older adults.

Indexed as

AdultAgedAgingCase-Control StudiesChronic DiseaseEnzyme ActivationExtracellular TrapsFemaleHumansImmunity, InnateInterleukin-8LipopolysaccharidesMaleMiddle AgedNeutrophilsp38 Mitogen-Activated Protein KinasesInterleukin-8Lipopolysaccharidesp38 Mitogen-Activated Protein KinasesReactive Oxygen SpeciesReceptors, Cell SurfaceTumor Necrosis Factor-alphaagingneutrophilneutrophil extracellular trapsperiodontitis

Identifiers

PMID24779584
PMCPMC4326942
OpenAlexW2001999580

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.