Evidence map›Paper›PMID 35132956›Full record

ArticleJCI insight2022

ADAM8 signaling drives neutrophil migration and ARDS severity.

Catharina Conrad, Daniela Yildiz, Simon J Cleary, Andreas Margraf, Lena Cook, Uwe Schlomann, Barry Panaretou, Jessica L Bowser, Harry Karmouty-Quintana, Jiwen Li and 20 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
5.0field-weighted citation impact, top 3% 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

27 citing papers in PubMed, 59 citations in OpenAlex.

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  15. Neutrophil reduction attenuates the severity of lung injury in the early phase of pneumococcal pneumonia in mice.American journal of physiology. Lung cellular and molecular physiology · 2024
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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

30 authors at 10 institutions in 3 countries.

Catharina ConradDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Daniela YildizInstitute of Experimental and Clinical Pharmacology and Toxicology, PZMS, ZHMB, Saarland University, Homburg, Germany.
Simon J ClearyDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Andreas MargrafDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
Lena CookDepartment of Neurosurgery/Lab, Faculty of Medicine, Philipps-University, Marburg, Germany.
Uwe SchlomannDepartment of Neurosurgery/Lab, Faculty of Medicine, Philipps-University, Marburg, Germany.
Barry PanaretouSchool of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom.
Jessica L BowserDepartment of Pathology & Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Harry Karmouty-QuintanaDepartment of Biochemistry and Molecular Biology, and.
Jiwen LiDepartment of Anesthesiology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Nathaniel K BergDepartment of Anesthesiology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Samuel C MartinDepartment of Chemistry, Rice University, Houston, Texas, USA.
Ahmad AljohmaniInstitute of Experimental and Clinical Pharmacology and Toxicology, PZMS, ZHMB, Saarland University, Homburg, Germany.
S Farshid Moussavi-HaramiDepartment of Pediatrics, Division of Pediatric Critical Care, University of California, San Francisco, San Francisco, California, USA.
Kristin M WangDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Jennifer J TianDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Mélia MagnenDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Colin ValetDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Longhui QiuDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Jonathan P SingerDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Holger K EltzschigDepartment of Anesthesiology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA.
CAPSys Study Group
Wilhelm BertramsInstitute for Lung Research (iLung), Philipps-University, Marburg, Germany.
Susanne HeroldDepartment of Internal Medicine II, University Medical Center Giessen and Marburg, Giessen, Germany.
Norbert SuttorpDepartment of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Bernd SchmeckDeutsches Zentrum für Lungenforschung (DZL), Giessen, Germany.
Zachary T BallDepartment of Chemistry, Rice University, Houston, Texas, USA.
Alexander ZarbockDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
Mark R LooneyDepartment of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Jörg W BartschDepartment of Neurosurgery/Lab, Faculty of Medicine, Philipps-University, Marburg, Germany.
University of California, San Francisco · USPhilipps University of Marburg · DEThe University of Texas Health Science Center · USRice University · USSaarland University · DEUniversitätsklinikum Gießen und Marburg · DEUniversity Hospital Münster · DECharité - Universitätsmedizin Berlin · DEKing's College London · GBUniversity of North Carolina at Chapel Hill · US

Funding

Immunobiology of the normal and injured lungR35HL161241 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARK ROBERTS LOONEY · 2022 to 2026
$4.2M
Mechanisms and pathogenicity of SARS-CoV-2-induced neutrophil extracellular trapsR01AI160167 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOONEY, MARK ROBERTS · 2021 to 2025
$3.1M
Sineoculis Homeobox Homolog 1 (Six1) in Pulmonary FibrosisR01HL157100 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KARMOUTY-QUINTANA, HARRY · 2021 to 2025
$2.8M
Fine-tuning the Neutrophilic Response to PneumoniaR01AI125445 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOONEY, MARK ROBERTS · 2016 to 2020
$2.2M
microRNA miR-147 Dampens Alveolar Epithelial Inflammation During ARDSR01HL154720 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ELTZSCHIG, HOLGER K. · 2021 to 2024
$2.2M
Innate Immune Mechanisms of Primary Graft Dysfunction after Lung TransplantationR01HL130324 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOONEY, MARK ROBERTS · 2016 to 2019
$2.2M
Targeting MicroRNA miR-122 for the Treatment of Perioperative Liver InjuryR01DK122796 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ELTZSCHIG, HOLGER K., JU, CYNTHIA · 2020 to 2023
$1.8M
MicroRNA Shuttling during Acute Respiratory Distress SyndromeR01HL133900 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ELTZSCHIG, HOLGER K. · 2017 to 2020
$1.5M
NHLBI NIH HHS R01 HL130324NHLBI NIH HHS R01 HL133900NHLBI NIH HHS R01 HL154720NHLBI NIH HHS R01 HL157100NHLBI NIH HHS R35 HL161241NIAID NIH HHS R01 AI125445NIAID NIH HHS R01 AI160167NIDDK NIH HHS R01 DK122796
6 · The paper itself

Abstract

Acute respiratory distress syndrome (ARDS) results in catastrophic lung failure and has an urgent, unmet need for improved early recognition and therapeutic development. Neutrophil influx is a hallmark of ARDS and is associated with the release of tissue-destructive immune effectors, such as matrix metalloproteinases (MMPs) and membrane-anchored metalloproteinase disintegrins (ADAMs). Here, we observed using intravital microscopy that Adam8-/- mice had impaired neutrophil transmigration. In mouse pneumonia models, both genetic deletion and pharmacologic inhibition of ADAM8 attenuated neutrophil infiltration and lung injury while improving bacterial containment. Unexpectedly, the alterations of neutrophil function were not attributable to impaired proteolysis but resulted from reduced intracellular interactions of ADAM8 with the actin-based motor molecule Myosin1f that suppressed neutrophil motility. In 2 ARDS cohorts, we analyzed lung fluid proteolytic signatures and identified that ADAM8 activity was positively correlated with disease severity. We propose that in acute inflammatory lung diseases such as pneumonia and ARDS, ADAM8 inhibition might allow fine-tuning of neutrophil responses for therapeutic gain.

Indexed as

Gene Expression RegulationADAM ProteinsAnimalsAntigens, CDCells, CulturedDisease Models, AnimalHumansMaleMembrane ProteinsMiceMice, Inbred C57BLMicroscopy, ConfocalRespiratory Distress SyndromeRNAAdam8 protein, mouseADAM ProteinsAntigens, CDMembrane ProteinsRNAInflammationInnate immunityNeutrophilsProteasesPulmonology

Identifiers

PMID35132956
PMCPMC8855804
OpenAlexW4210658082

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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.