Evidence map›Paper›PMID 34650553›Full record

ArticleFrontiers in immunology2021

Internalization of the Membrane Attack Complex Triggers NLRP3 Inflammasome Activation and IL-1β Secretion in Human Macrophages.

Ines Diaz-Del-Olmo, Jonathan Worboys, Fatima Martin-Sanchez, Anna Gritsenko, Ashley R Ambrose, Gillian M Tannahill, Eva-Maria Nichols, Gloria Lopez-Castejon, Daniel M Davis

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

27 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
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  9. Disseminated intravascular coagulation.Journal of intensive care · 2025
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  11. Is the endotoxin-complement cascade the major driver in lipedema?Trends in endocrinology and metabolism: TEM · 2024
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  13. Constituents fromMolecules (Basel, Switzerland) · 2024
    Article
  14. Review
  15. Review
  16. Article
  17. Article
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  20. Gasdermins in sepsis.Frontiers in immunology · 2023
    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

9 authors at 2 institutions in 1 country.

Ines Diaz-Del-OlmoDivision of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United Kingdom.
Jonathan WorboysDivision of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United Kingdom.
Fatima Martin-SanchezDivision of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United Kingdom.
Anna GritsenkoDivision of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United Kingdom.
Ashley R AmbroseDivision of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United Kingdom.
Gillian M TannahillAdaptive Immunity Research Unit, GSK, Stevenage, United Kingdom.
Eva-Maria NicholsAdaptive Immunity Research Unit, GSK, Stevenage, United Kingdom.
Gloria Lopez-CastejonDivision of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United Kingdom.
Daniel M DavisDivision of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United Kingdom.
University of Manchester · GBAge UK · GB

Funding

Wellcome TrustWellcome Trust 104192/Z/14/ZWellcome Trust 110091/Z/15/Z
6 · The paper itself

Abstract

Interleukin 1β (IL-1β) plays a major role in inflammation and is secreted by immune cells, such as macrophages, upon recognition of danger signals. Its secretion is regulated by the inflammasome, the assembly of which results in caspase 1 activation leading to gasdermin D (GSDMD) pore formation and IL-1β release. During inflammation, danger signals also activate the complement cascade, resulting in the formation of the membrane attack complex (MAC). Here, we report that stimulation of LPS-primed human macrophages with sub-lytic levels of MAC results in activation of the NOD-like receptor 3 (NLRP3) inflammasome and GSDMD-mediated IL-1β release. The MAC is first internalized into endosomes and then colocalizes with inflammasome components; adapter protein apoptosis associated speck-like protein containing a CARD (ASC) and NLRP3. Pharmacological inhibitors established that MAC-triggered activation of the NLRP3 inflammasome was dependent on MAC endocytosis. Internalization of the MAC also caused dispersion of the trans-Golgi network. Thus, these data uncover a role for the MAC in activating the inflammasome and triggering IL-1β release in human macrophages.

Indexed as

BiomarkersCell LineCells, CulturedComplement Membrane Attack ComplexComplement System ProteinsEndocytosisEndosomesHumansInflammasomesInterleukin-1betaMacrophage ActivationMacrophagesModels, BiologicalNLR Family, Pyrin Domain-Containing 3 ProteinProtein TransportBiomarkersComplement Membrane Attack ComplexComplement System ProteinsIL1B protein, humanInflammasomesInterleukin-1betaNLR Family, Pyrin Domain-Containing 3 ProteincomplementIL-1βinflammasomemacrophagemembrane attack complexNLRP3

Identifiers

PMID34650553
PMCPMC8506164
OpenAlexW3203074555

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.