Evidence map›Paper›PMID 30942918›Full record

ArticleJournal of leukocyte biology2019

Neutrophil GM-CSF receptor dynamics in acute lung injury.

Silvia De Alessandris, G John Ferguson, Alison J Dodd, Jatinder K Juss, Abhinandan Devaprasad, Siân Piper, Owen Wyatt, Helen Killick, Dominic J Corkill, E Suzanne Cohen and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of leukocyte biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 15% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

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  15. Frontiers in immunology · 2022
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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

18 authors at 3 institutions in 2 countries.

Silvia De AlessandrisDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
G John FergusonRespiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom.
Alison J DoddRespiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom.
Jatinder K JussDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Abhinandan DevaprasadDepartment of Rheumatology and Clinical Immunology and Laboratory of Translational Immunology, University Medical Centre, Utrecht, Netherlands.
Siân PiperRespiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom.
Owen WyattRespiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom.
Helen KillickRespiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom.
Dominic J CorkillRespiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom.
E Suzanne CohenRespiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom.
Aridaman PanditDepartment of Rheumatology and Clinical Immunology and Laboratory of Translational Immunology, University Medical Centre, Utrecht, Netherlands.
Timothy R D J RadstakeDepartment of Rheumatology and Clinical Immunology and Laboratory of Translational Immunology, University Medical Centre, Utrecht, Netherlands.
Rosalind SimmondsDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Alison M CondliffeDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Matthew A SleemanRespiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom.
Andrew S CowburnDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Donna K FinchRespiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom.ORCID 0000-0003-1834-1260
Edwin R ChilversDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Aimmune Therapeutics (United Kingdom) · GBUniversity of Cambridge · GBUniversity Medical Center Utrecht · NL

Funding

Wellcome Trust
6 · The paper itself

Abstract

GM-CSF is important in regulating acute, persistent neutrophilic inflammation in certain settings, including lung injury. Ligand binding induces rapid internalization of the GM-CSF receptor (GM-CSFRα) complex, a process essential for signaling. Whereas GM-CSF controls many aspects of neutrophil biology, regulation of GM-CSFRα expression is poorly understood, particularly the role of GM-CSFRα in ligand clearance and whether signaling is sustained despite major down-regulation of GM-CSFRα surface expression. We established a quantitative assay of GM-CSFRα surface expression and used this, together with selective anti-GM-CSFR antibodies, to define GM-CSFRα kinetics in human neutrophils, and in murine blood and alveolar neutrophils in a lung injury model. Despite rapid sustained ligand-induced GM-CSFRα loss from the neutrophil surface, which persisted even following ligand removal, pro-survival effects of GM-CSF required ongoing ligand-receptor interaction. Neutrophils recruited to the lungs following LPS challenge showed initially high mGM-CSFRα expression, which along with mGM-CSFRβ declined over 24 hr; this was associated with a transient increase in bronchoalveolar lavage fluid (BALF) mGM-CSF concentration. Treating mice in an LPS challenge model with CAM-3003, an anti-mGM-CSFRα mAb, inhibited inflammatory cell influx into the lung and maintained the level of BALF mGM-CSF. Consistent with neutrophil consumption of GM-CSF, human neutrophils depleted exogenous GM-CSF, independent of protease activity. These data show that loss of membrane GM-CSFRα following GM-CSF exposure does not preclude sustained GM-CSF/GM-CSFRα signaling and that this receptor plays a key role in ligand clearance. Hence neutrophilic activation via GM-CSFR may play an important role in neutrophilic lung inflammation even in the absence of high GM-CSF levels or GM-CSFRα expression.

Indexed as

Acute Lung InjuryAdultAnimalsCell Line, TumorCytokine Receptor Common beta SubunitDisease Models, AnimalFemaleGene Expression RegulationHumansLipopolysaccharidesMaleMiceMice, Inbred BALB CMice, TransgenicNeutrophilsPulmonary AlveoliCsf2ra protein, mouseCytokine Receptor Common beta SubunitGM-CSF receptor-alpha subunit, humanLipopolysaccharidesReceptors, Granulocyte-Macrophage Colony-Stimulating FactoralveolarapoptosisinflammationLPSsignaling

Identifiers

PMID30942918
PMCPMC6850700
OpenAlexW2925961191

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.