Evidence map›Paper›PMID 30796192›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Calpain drives pyroptotic vimentin cleavage, intermediate filament loss, and cell rupture that mediates immunostimulation.

Michael A Davis, Marian R Fairgrieve, Andreas Den Hartigh, Olga Yakovenko, Bhargavi Duvvuri, Christian Lood, Wendy E Thomas, Susan L Fink, Michael Gale

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

68 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
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  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Involvement of the pyroptosis-HMGB1 axis in systemic diseases.Frontiers in cell and developmental biology · 2026
    Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Annexin A2 Contributes to Release of Extracellular Vimentin in Response to Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  17. Review
  18. Article
  19. Article
  20. Review

8 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

9 authors.

Michael A DavisDepartment of Immunology, University of Washington, Seattle, WA 98109.ORCID 0000-0002-5406-4128
Marian R FairgrieveDepartment of Immunology, University of Washington, Seattle, WA 98109.
Andreas Den HartighDepartment of Laboratory Medicine, University of Washington, Seattle, WA 98195.
Olga YakovenkoDepartment of Bioengineering, University of Washington, Seattle, WA 98195.
Bhargavi DuvvuriDivision of Rheumatology, University of Washington, Seattle, WA 98109.
Christian LoodDivision of Rheumatology, University of Washington, Seattle, WA 98109.
Wendy E ThomasDepartment of Bioengineering, University of Washington, Seattle, WA 98195.ORCID 0000-0001-8602-0819
Susan L FinkDepartment of Laboratory Medicine, University of Washington, Seattle, WA 98195.
Michael GaleDepartment of Immunology, University of Washington, Seattle, WA 98109; mgale@uw.edu.

Funding

Unlocking Zika Virus Immune Control and Pathogenesis with the Collaborative CrossU19AI100625 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, HEISE, MARK T · 2012 to 2021
$36.6M
Innate Immune Control of West Nile VirusR01AI104002 · NIAID · UNIVERSITY OF WASHINGTON · PI DIAMOND, MICHAEL S, GALE, MICHAEL · 2013 to 2017
$3.7M
Mechanisms for ligand binding by serine-rich adhesins of Gram-positive pathogensR01AI106987 · NIAID · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI IVERSON, T M, SULLAM, PAUL M. · 2014 to 2018
$3.4M
Mechanisms of hepatic innate immune activation by HCVR01AI127463 · NIAID · UNIVERSITY OF WASHINGTON · PI GALE, MICHAEL, ROSEN, HUGO RAMON · 2017 to 2021
$2.8M
The Host Response to Hepatitis C VirusR01AI118916 · NIAID · UNIVERSITY OF WASHINGTON · PI GALE, MICHAEL · 2016 to 2020
$2.5M
Role of Ire1alpha in Resistance to Viral-Induced ApoptosisK08AI119142 · NIAID · YALE UNIVERSITY · PI FINK, SUSAN LEILANI · 2015 to 2019
$922k
NIAID NIH HHS K08 AI119142NIAID NIH HHS R01 AI104002NIAID NIH HHS R01 AI106987NIAID NIH HHS R01 AI118916NIAID NIH HHS R01 AI127463NIAID NIH HHS U19 AI100625
6 · The paper itself

Abstract

Pyroptosis is an inflammatory form of programmed cell death following cellular damage or infection. It is a lytic process driven by gasdermin D-mediated cellular permeabilization and presumed osmotic forces thought to induce swelling and rupture. We found that pyroptotic cells do not spontaneously rupture in culture but lose mechanical resilience. As a result, cells were susceptible to rupture by extrinsic forces, such as shear stress or compression. Cell analyses revealed that all major cytoskeleton components were disrupted during pyroptosis and that sensitivity to rupture was calpain-dependent and linked with cleavage of vimentin and loss of intermediate filaments. Moreover, while release of lactate dehydrogenase (LDH), HMGB1, and IL-1β occurred without rupture, rupture was required for release of large inflammatory stimuli-ASC specks, mitochondria, nuclei, and bacteria. Importantly, supernatants from ruptured cells were more immunostimulatory than those from nonruptured cells. These observations reveal undiscovered cellular events occurring during pyroptosis, define the mechanisms driving pyroptotic rupture, and highlight the immunologic importance of this event.

Indexed as

ImmunizationPyroptosisAlarminsCalpainCARD Signaling Adaptor ProteinsCaspase 1Compressive StrengthCytoskeletonCytosolGasderminsHumansInflammasomesIntermediate FilamentsIntracellular Signaling Peptides and ProteinsNeoplasm ProteinsPhosphate-Binding ProteinsAlarminsCalpainCARD Signaling Adaptor ProteinsCaspase 1GasderminsGSDMD protein, humanInflammasomesIntracellular Signaling Peptides and ProteinsNeoplasm ProteinsPhosphate-Binding ProteinsPYCARD protein, humanVimentincalpainintermediate filamentspyroptosisrupturevimentin

Identifiers

PMID30796192
PMCPMC6421439

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.