ADAM8 signaling drives neutrophil migration and ARDS severity

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dc.citation.articleNumbere149870en_US
dc.citation.issueNumber3en_US
dc.citation.journalTitleJCI Insighten_US
dc.citation.volumeNumber7en_US
dc.contributor.authorConrad, Catharinaen_US
dc.contributor.authorYildiz, Danielaen_US
dc.contributor.authorCleary, Simon J.en_US
dc.contributor.authorMargraf, Andreasen_US
dc.contributor.authorCook, Lenaen_US
dc.contributor.authorSchlomann, Uween_US
dc.contributor.authorPanaretou, Barryen_US
dc.contributor.authorBowser, Jessica L.en_US
dc.contributor.authorKarmouty-Quintana, Harryen_US
dc.contributor.authorLi, Jiwenen_US
dc.contributor.authorBerg, Nathaniel K.en_US
dc.contributor.authorMartin, Samuel C.en_US
dc.contributor.authorAljohmani, Ahmaden_US
dc.contributor.authorMoussavi-Harami, S. Farshiden_US
dc.contributor.authorWang, Kristin M.en_US
dc.contributor.authorTian, Jennifer J.en_US
dc.contributor.authorMagnen, Méliaen_US
dc.contributor.authorValet, Colinen_US
dc.contributor.authorQiu, Longhuien_US
dc.contributor.authorSinger, Jonathan P.en_US
dc.contributor.authorEltzschig, Holger K.en_US
dc.contributor.authorBertrams, Wilhelmen_US
dc.contributor.authorHerold, Susanneen_US
dc.contributor.authorSuttorp, Norberten_US
dc.contributor.authorSchmeck, Bernden_US
dc.contributor.authorBall, Zachary T.en_US
dc.contributor.authorZarbock, Alexanderen_US
dc.contributor.authorLooney, Mark R.en_US
dc.contributor.authorBartsch, Jörg W.en_US
dc.date.accessioned2022-03-24T13:31:32Zen_US
dc.date.available2022-03-24T13:31:32Zen_US
dc.date.issued2022en_US
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.en_US
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.en_US
dc.identifier.digital149870-1-20220120113113en_US
dc.identifier.doihttps://doi.org/10.1172/jci.insight.149870en_US
dc.identifier.urihttps://hdl.handle.net/1911/112027en_US
dc.language.isoengen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.rightsThis work is licensed under the Creative Commons Attribution 4.0 International License.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleADAM8 signaling drives neutrophil migration and ARDS severityen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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