Evidence map›Paper›PMID 32730588›Full record

ArticleBlood2020

The integrin-linked kinase is required for chemokine-triggered high-affinity conformation of the neutrophil β2-integrin LFA-1.

Andreas Margraf, Giulia Germena, Hannes C A Drexler, Jan Rossaint, Nadine Ludwig, Barbara Prystaj, Sina Mersmann, Katharina Thomas, Helena Block, Wiebke Gottschlich and 8 more

Abstract read
PubMed Publisher
In one paragraph

Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

31 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
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  6. Kindlin-3 phosphorylation is crucial for thrombosis and hemostasisResearch and practice in thrombosis and haemostasis · 2025
    Article
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  8. Neutrophils-biology and diversity.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 2 countries.

Andreas MargrafDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Giulia GermenaDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Hannes C A DrexlerMax Planck Institute for Molecular Biomedicine, Muenster, Germany.
Jan RossaintDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Nadine LudwigDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Barbara PrystajDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Sina MersmannDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Katharina ThomasDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Helena BlockDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Wiebke GottschlichDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Chang LiuDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Peter W KrennDepartment of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
Hermann HallerDepartment of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
Barbara HeitplatzGerhard Domagk Institute of Pathology, University Hospital Muenster, Muenster, Germany; and.
Marika Meyer Zu BrickweddeMax Planck Institute for Molecular Biomedicine, Muenster, Germany.
Markus MoserCenter for Translational Cancer Research, TUM School of Medicine, Technische Universität München, Munich, Germany.
Dietmar VestweberMax Planck Institute for Molecular Biomedicine, Muenster, Germany.
Alexander ZarbockDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
University Hospital Münster · DEMax Planck Institute for Molecular Biomedicine · DEMax Planck Institute of Biochemistry · DEMedizinische Hochschule Hannover · DETechnical University of Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neutrophil adhesion and extravasation into tissue at sites of injury or infection depend on binding of the integrin lymphocyte function-associated antigen 1 (LFA-1) to ICAM-1 expressed on activated endothelial cells. The activation-dependent conformational change of LFA-1 to the high-affinity conformation (H+) requires kindlin-3 binding to the β2-integrin cytoplasmic domain. Here we show that genetic deletion of the known kindlin interactor integrin-linked kinase (ILK) impaired neutrophil adhesion and extravasation in the cremaster muscle and in a clinically relevant model of renal ischemia reperfusion injury. Using in vitro microfluidic adhesion chambers and conformation-specific antibodies, we show that knockdown of ILK in HL-60 cells reduced the conformational change of β2-integrins to the H+ conformation. Mechanistically, we found that ILK was required for protein kinase C (PKC) membrane targeting and chemokine-induced upregulation of its kinase activity. Moreover, PKC-α deficiency also resulted in impaired leukocyte adhesion in bone marrow chimeric mice. Mass spectrometric and western blot analyses revealed stimulation- and ILK-dependent phosphorylation of kindlin-3 upon activation. In summary, our data indicate an important role of ILK in kindlin-3-dependent conformational activation of LFA-1.

Indexed as

Acute Kidney InjuryAnimalsCD18 AntigensCell AdhesionChemokinesDisease Models, AnimalHL-60 CellsHumansLeukocytesLymphocyte Function-Associated Antigen-1Membrane ProteinsMiceNeoplasm ProteinsNeutrophilsPhosphorylationProtein Kinase CCD18 AntigensChemokinesFERMT3 protein, humanLymphocyte Function-Associated Antigen-1Membrane ProteinsNeoplasm ProteinsProtein Kinase CProtein Serine-Threonine KinasesScaffold Protein ILK

Identifiers

PMID32730588
OpenAlexW3046406187

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.