ADAM8 signaling drives neutrophil migration and ARDS severity

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dc.citation.articleNumbere149870
dc.citation.issueNumber3
dc.citation.journalTitleJCI Insight
dc.citation.volumeNumber7
dc.contributor.authorConrad, Catharina
dc.contributor.authorYildiz, Daniela
dc.contributor.authorCleary, Simon J.
dc.contributor.authorMargraf, Andreas
dc.contributor.authorCook, Lena
dc.contributor.authorSchlomann, Uwe
dc.contributor.authorPanaretou, Barry
dc.contributor.authorBowser, Jessica L.
dc.contributor.authorKarmouty-Quintana, Harry
dc.contributor.authorLi, Jiwen
dc.contributor.authorBerg, Nathaniel K.
dc.contributor.authorMartin, Samuel C.
dc.contributor.authorAljohmani, Ahmad
dc.contributor.authorMoussavi-Harami, S. Farshid
dc.contributor.authorWang, Kristin M.
dc.contributor.authorTian, Jennifer J.
dc.contributor.authorMagnen, Mélia
dc.contributor.authorValet, Colin
dc.contributor.authorQiu, Longhui
dc.contributor.authorSinger, Jonathan P.
dc.contributor.authorEltzschig, Holger K.
dc.contributor.authorBertrams, Wilhelm
dc.contributor.authorHerold, Susanne
dc.contributor.authorSuttorp, Norbert
dc.contributor.authorSchmeck, Bernd
dc.contributor.authorBall, Zachary T.
dc.contributor.authorZarbock, Alexander
dc.contributor.authorLooney, Mark R.
dc.contributor.authorBartsch, Jörg W.
dc.date.accessioned2022-03-24T13:31:32Z
dc.date.available2022-03-24T13:31:32Z
dc.date.issued2022
dc.description.abstractAcute 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.
dc.identifier.citationConrad, Catharina, Yildiz, Daniela, Cleary, Simon J., et al.. "ADAM8 signaling drives neutrophil migration and ARDS severity." <i>JCI Insight,</i> 7, no. 3 (2022) American Society for Clinical Investigation: https://doi.org/10.1172/jci.insight.149870.
dc.identifier.digital149870-1-20220120113113
dc.identifier.doihttps://doi.org/10.1172/jci.insight.149870
dc.identifier.urihttps://hdl.handle.net/1911/112027
dc.language.isoeng
dc.publisherAmerican Society for Clinical Investigation
dc.rightsThis work is licensed under the Creative Commons Attribution 4.0 International License.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleADAM8 signaling drives neutrophil migration and ARDS severity
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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