Evidence map›Paper›PMID 27578049›Full record

ArticleNature communications2016

Neutrophil recruitment limited by high-affinity bent β2 integrin binding ligand in cis.

Zhichao Fan, Sara McArdle, Alex Marki, Zbigniew Mikulski, Edgar Gutierrez, Britta Engelhardt, Urban Deutsch, Mark Ginsberg, Alex Groisman, Klaus Ley

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

74 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Targeting Neutrophil βBiomolecules · 2023
    Review
  15. Article
  16. Review
  17. Review
  18. Advances in NK cell therapy for brain tumors.NPJ precision oncology · 2023
    Review
  19. Article
  20. Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023
    Review

14 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

10 authors at 3 institutions in 2 countries.

Zhichao FanDivision of Inflammation Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle Drive, La Jolla, California 92037, USA.ORCID 0000-0001-5385-9626
Sara McArdleDivision of Inflammation Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle Drive, La Jolla, California 92037, USA.
Alex MarkiDivision of Inflammation Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle Drive, La Jolla, California 92037, USA.
Zbigniew MikulskiDivision of Inflammation Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle Drive, La Jolla, California 92037, USA.
Edgar GutierrezDepartment of Physics, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Britta EngelhardtTheodor Kocher Institute, University of Bern, 1 Freiestrasse, 3012 Bern, Switzerland.
Urban DeutschTheodor Kocher Institute, University of Bern, 1 Freiestrasse, 3012 Bern, Switzerland.
Mark GinsbergDepartment of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.ORCID 0000-0002-5685-5417
Alex GroismanDepartment of Physics, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Klaus LeyDivision of Inflammation Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle Drive, La Jolla, California 92037, USA.
La Jolla Institute for Immunology · USUniversity of California San Diego · USUniversity of Bern · CH

Funding

The Interaction of TPO and Integrins in Hematopoiesis CellsP01HL078784 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2005 to 2019
$28.3M
American Heart Association-American Stroke Association 16POST31160014NHLBI NIH HHS P01 HL078784
6 · The paper itself

Abstract

Neutrophils are essential for innate immunity and inflammation and many neutrophil functions are β2 integrin-dependent. Integrins can extend (E(+)) and acquire a high-affinity conformation with an 'open' headpiece (H(+)). The canonical switchblade model of integrin activation proposes that the E(+) conformation precedes H(+), and the two are believed to be structurally linked. Here we show, using high-resolution quantitative dynamic footprinting (qDF) microscopy combined with a homogenous conformation-reporter binding assay in a microfluidic device, that a substantial fraction of β2 integrins on human neutrophils acquire an unexpected E(-)H(+) conformation. E(-)H(+) β2 integrins bind intercellular adhesion molecules (ICAMs) in cis, which inhibits leukocyte adhesion in vitro and in vivo. This endogenous anti-inflammatory mechanism inhibits neutrophil aggregation, accumulation and inflammation.

Indexed as

Neutrophil InfiltrationAnimalsBone Marrow TransplantationCD18 AntigensCell Adhesion MoleculesHealthy VolunteersHumansImaging, Three-DimensionalInflammationIntravital MicroscopyLigandsMaleMiceMice, Inbred C57BLMice, KnockoutMolecular ImagingCD18 AntigensCell Adhesion MoleculesLigandsRecombinant Proteins

Identifiers

PMID27578049
PMCPMC5013657
OpenAlexW2510806142

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.