Evidence map›Paper›PMID 27006116›Full record

ArticleJournal of cell science2016

Complement-mediated 'bystander' damage initiates host NLRP3 inflammasome activation.

Rahul Suresh, Prabha Chandrasekaran, Fayyaz S Sutterwala, David M Mosser

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

Article in Journal of cell science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 67 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. The complement system in autoimmune diseases: pathogenesis, diagnostic markers, and therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. NLRP3 inflammasome in neurodegenerative disease.Translational research : the journal of laboratory and clinical medicine · 2023
    Review
  13. Review
  14. Review
  15. Review
  16. Neutrophils activated by membrane attack complexes increase the permeability of melanoma blood vessels.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  17. Article
  18. Review
  19. Article
  20. 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

4 authors at 2 institutions in 1 country.

Rahul SureshDepartment of Cell Biology and Molecular Genetics and the Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742, USA.
Prabha ChandrasekaranDepartment of Cell Biology and Molecular Genetics and the Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742, USA.
Fayyaz S SutterwalaThe Inflammation Program, Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, IA 52241, USA.
David M MosserDepartment of Cell Biology and Molecular Genetics and the Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742, USA dmosser@umd.edu.ORCID 0000-0002-9503-4187
University of Maryland, College Park · USUniversity of Iowa · US

Funding

Regulatory macrophages and the host inflammatory responseR01GM102589 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI MOSSER, DAVID M · 2013 to 2016
$1.2M
NIGMS NIH HHS R01 GM102589
6 · The paper itself

Abstract

Complement activation has long been associated with inflammation, primarily due to the elaboration of the complement anaphylotoxins C5a and C3a. In this work, we demonstrate that the phagocytosis of complement-opsonized particles promotes host inflammatory responses by a new mechanism that depends on the terminal complement components (C5b-C9). We demonstrate that during the phagocytosis of complement-opsonized particles, the membrane attack complex (MAC) of complement can be transferred from the activating particle to the macrophage plasma membrane by a 'bystander' mechanism. This MAC-mediated bystander damage initiates NLRP3 inflammasome activation, resulting in caspase-1 activation and IL-1β and IL-18 secretion. Inflammasome activation is not induced when macrophages phagocytize unopsonized particles or particles opsonized with serum deficient in one of the terminal complement components. The secretion of IL-1β and IL-18 by macrophages depends on NLRP3, ASC (also known as PYCARD) and caspase-1, as macrophages deficient in any one of these components fail to secrete these cytokines following phagocytosis. The phagocytosis of complement-opsonized particles increases leukocyte recruitment and promotes T helper 17 cell (TH17) biasing. These findings reveal a new mechanism by which complement promotes inflammation and regulates innate and adaptive immunity.

Indexed as

AnimalsApoptosis Regulatory ProteinsBystander EffectCARD Signaling Adaptor ProteinsComplement C3aComplement C5aComplement Membrane Attack ComplexHEK293 CellsHumansInterleukin-18Interleukin-1betaMacrophagesMiceMice, Inbred BALB CMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsComplement C3aComplement C5aComplement Membrane Attack ComplexIL1B protein, mouseInterleukin-18Interleukin-1betaNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePycard protein, mouseASCBystander activationCaspaseComplementIL-18IL-1βInflammasomeMembrane attack complexNLRP3PhagocytosisTH17

Identifiers

PMID27006116
PMCPMC4893798
OpenAlexW2306491320

What OpenQuestion holds

Textmetadata
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.