Evidence map›Paper›PMID 29410422›Full record

ArticleNature communications2018

A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense.

Dennis Wolf, Nathaly Anto-Michel, Hermann Blankenbach, Ansgar Wiedemann, Konrad Buscher, Jan David Hohmann, Bock Lim, Marina Bäuml, Alex Marki, Maximilian Mauler and 22 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

70 citing papers in PubMed, 100 citations in OpenAlex.

  1. Review
  2. Inhibition of CD154:CD11b interactions using a novel nanotherapeutic improves allograft survival.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026
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  13. Differential induction of donor-reactive Foxp3American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024
    Article
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  16. Review
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  19. Article
  20. Article

10 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

32 authors at 7 institutions in 4 countries.

Dennis WolfCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.ORCID http://orcid.org/0000-0003-1525-4348
Nathaly Anto-MichelCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Hermann BlankenbachCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Ansgar WiedemannCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Konrad BuscherInflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
Jan David HohmannAtherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, 8008, VIC, Australia.
Bock LimAtherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, 8008, VIC, Australia.
Marina BäumlCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Alex MarkiInflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
Maximilian MaulerCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Daniel DuerschmiedCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Zhichao FanInflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0001-5385-9626
Holger WinkelsInflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
Daniel SidlerDivision of Nephrology, Inselspital, Bern University Hospital, Bern, 3010, Switzerland.
Philipp DiehlCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Dirk M ZajoncDivision of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
Ingo HilgendorfCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Peter StachonCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Timoteo MarchiniCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Florian WilleckeCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Maximilian SchellCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Björn SommerNeurosurgery, Medical Faculty of the University of Erlangen, Erlangen, 91054, Germany.
Constantin von Zur MuhlenCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Jochen ReinöhlCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Teresa GerhardtInflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
Edward F PlowDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Valentin YakubenkoDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Peter LibbyBrigham and Women's Hospital, Cardiovascular Medicine, Harvard Medical School, Boston, MA, 02115, USA.
Christoph BodeCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
Klaus LeyInflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
Karlheinz PeterAtherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, 8008, VIC, Australia. karlheinz.peter@baker.edu.au.
Andreas ZirlikCardiology and Angiology I, University Heart Center, and Medical Faculty, University of Freiburg, Freiburg, 79106, Germany.
University of Freiburg · DELa Jolla Institute for Immunology · USBaker Heart and Diabetes Institute · AUCleveland Clinic Lerner College of Medicine · USBrigham and Women's Hospital · USFriedrich-Alexander-Universität Erlangen-Nürnberg · DEUniversity Hospital 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
Structural Determinants Of Ceruloplasmin Inflammatory ActivityP01HL076491 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI PLOW, EDWARD FRANKLIN · 2004 to 2019
$27.3M
Activation of the beta-3 integrins: Role of the KindlinsR01HL096062 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI PLOW, EDWARD FRANKLIN · 2009 to 2022
$5.6M
The role of β2 integrins in macrophage retention and egress during inflammationR01DK102020 · NIDDK · EAST TENNESSEE STATE UNIVERSITY · PI YAKUBENKO, VALENTIN P · 2014 to 2017
$1.2M
NHLBI NIH HHS P01 HL076491NHLBI NIH HHS P01 HL078784NHLBI NIH HHS R01 HL096062NIDDK NIH HHS R01 DK102020
6 · The paper itself

Abstract

Integrin-based therapeutics have garnered considerable interest in the medical treatment of inflammation. Integrins mediate the fast recruitment of monocytes and neutrophils to the site of inflammation, but are also required for host defense, limiting their therapeutic use. Here, we report a novel monoclonal antibody, anti-M7, that specifically blocks the interaction of the integrin Mac-1 with its pro-inflammatory ligand CD40L, while not interfering with alternative ligands. Anti-M7 selectively reduces leukocyte recruitment in vitro and in vivo. In contrast, conventional anti-Mac-1 therapy is not specific and blocks a broad repertoire of integrin functionality, inhibits phagocytosis, promotes apoptosis, and fuels a cytokine storm in vivo. Whereas conventional anti-integrin therapy potentiates bacterial sepsis, bacteremia, and mortality, a ligand-specific intervention with anti-M7 is protective. These findings deepen our understanding of ligand-specific integrin functions and open a path for a new field of ligand-targeted anti-integrin therapy to prevent inflammatory conditions.

Indexed as

AnimalsAntibodies, MonoclonalBinding SitesCD40 LigandHost-Pathogen InteractionsHumansInflammationLeukocytesMacrophage-1 AntigenMaleMice, Inbred C57BLMolecular Targeted TherapyNeutrophilsSepsisAntibodies, MonoclonalCD40 LigandMacrophage-1 Antigen

Identifiers

PMID29410422
PMCPMC5802769
OpenAlexW2802586307

What OpenQuestion holds

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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.