Evidence map›Paper›PMID 23144497›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2012

Leukocyte function antigen-1, kindlin-3, and calcium flux orchestrate neutrophil recruitment during inflammation.

Neha Dixit, Min-Ho Kim, Jan Rossaint, Itsukyo Yamayoshi, Alexander Zarbock, Scott I Simon

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2012. 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
1.6field-weighted citation impact, top 20% 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, 66 citations in OpenAlex.

  1. Trial
  2. Article
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  4. Article
  5. Modulation of Neutrophil Recruitment and Inflammatory Signaling in Acute Respiratory Distress Syndrome by Leukotriene Inhibitors Montelukast and Zileuton.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. βCells · 2022
    Article
  13. Article
  14. Review
  15. Neutrophil Immunomodulatory Activity of Farnesene, a Component ofPharmaceuticals (Basel, Switzerland) · 2022
    Article
  16. Article
  17. Article
  18. Visualization of integrin molecules by fluorescence imaging and techniques.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2021
    Article
  19. Article
  20. ORAI1 and ORAI2 modulate murine neutrophil calcium signaling, cellular activation, and host defense.Proceedings of the National Academy of Sciences of the United States of America · 2020
    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

6 authors at 3 institutions in 2 countries.

Neha DixitDepartment of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
Min-Ho Kim
Jan Rossaint
Itsukyo Yamayoshi
Alexander Zarbock
Scott I Simon
University of California, Davis · USMax Planck Institute for Molecular Biomedicine · DEUniversity Hospital Münster · DE

Funding

Outside-in Mechanotransduced Inflammatory TargetsR01AI047294 · NIAID · UNIVERSITY OF CALIFORNIA DAVIS · PI SIMON, SCOTT IRWIN · 1999 to 2021
$7.0M
NIAID NIH HHS R01 AI047294
6 · The paper itself

Abstract

Neutrophil arrest and migration on inflamed endothelium involves a conformational shift in CD11a/CD18 (leukocyte function antigen-1; LFA-1) to a high-affinity and clustered state that determines the strength and lifetime of bond formation with ICAM-1. Cytoskeletal adapter proteins Kindlin-3 and Talin-1 anchor clustered LFA-1 to the cytoskeleton and facilitate the transition from neutrophil rolling to arrest. We recently reported that tensile force acts on LFA-1 bonds inducing their colocalization with Orai1, the predominant membrane store operated Ca(2+) channel that cooperates with the endoplasmic reticulum to elicit cytosolic flux. Because Kindlin-3 was recently reported to initiate LFA-1 clustering in lymphocytes, we hypothesized that it cooperates with Orai1 and LFA-1 in signaling local Ca(2+) flux necessary for shear-resistant neutrophil arrest. Using microfluidic flow channels combined with total internal reflection fluorescence microscopy, we applied defined shear stress to low- or high-affinity LFA-1 and imaged the spatiotemporal regulation of bond formation with Kindlin-3 recruitment and Ca(2+) influx. Orai1 and Kindlin-3 genes were silenced in neutrophil-like HL-60 cells to assess their respective roles in this process. Kindlin-3 was enriched within focal clusters of high-affinity LFA-1, which promoted physical linkage with Orai1. This macromolecular complex functioned to amplify inside-out Ca(2+) signaling in response to IL-8 stimulation by catalyzing an increased density of Talin-1 and consolidating LFA-1 clusters within sites of contact with ICAM-1. In this manner, neutrophils use focal adhesions as mechanosensors that convert shear stress-mediated tensile force into local bursts of Ca(2+) influx that catalyze cytoskeletal engagement and an adhesion-strengthened migratory phenotype.

Indexed as

AnimalsCalcium SignalingCell AdhesionCytoskeletal ProteinsGene Knockout TechniquesHL-60 CellsHumansHydrodynamicsInflammationLymphocyte Function-Associated Antigen-1Membrane ProteinsMiceMice, Inbred ICRNeoplasm ProteinsNeutrophil InfiltrationStress, PhysiologicalCytoskeletal ProteinsFERMT3 protein, humankindlin-3 protein, mouseLymphocyte Function-Associated Antigen-1Membrane ProteinsNeoplasm Proteins

Identifiers

PMID23144497
PMCPMC3723394
OpenAlexW2159392753

What OpenQuestion holds

Textmetadata
LicenceTDM
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.