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doi:10.22028/D291-37161
Titel: | ADAM8 signaling drives neutrophil migration and ARDS severity |
VerfasserIn: | Conrad, Catharina Yildiz, Daniela Cleary, Simon J. Margraf, Andreas Cook, Lena Schlomann, Uwe Panaretou, Barry Bowser, Jessica L. Karmouty-Quintana, Harry Li, Jiwen Berg, Nathaniel K. Martin, Samuel C. Aljohmani, Ahmad Moussavi-Harami, S. Farshid Wang, Kristin M Tian, Jennifer J. Magnen, Mélia Valet, Colin Qiu, Longhui Singer, Jonathan P. Eltzschig, Holger K. Bertrams, Wilhelm Herold, Susanne Suttorp, Norbert Schmeck, Bernd Ball, Zachary T. Zarbock, Alexander Looney, Mark R. Bartsch, Jörg W. |
Sprache: | Englisch |
Titel: | JCI insight |
Bandnummer: | 7 |
Heft: | 3 |
Verlag/Plattform: | American Society for Clinical Investigation |
Erscheinungsjahr: | 2022 |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
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. |
DOI der Erstveröffentlichung: | 10.1172/jci.insight.149870 |
URL der Erstveröffentlichung: | https://insight.jci.org/articles/view/149870 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-371611 hdl:20.500.11880/33721 http://dx.doi.org/10.22028/D291-37161 |
ISSN: | 2379-3708 |
Datum des Eintrags: | 6-Sep-2022 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplemental material |
In Beziehung stehendes Objekt: | https://insight.jci.org/articles/view/149870/sd/1 https://insight.jci.org/articles/view/149870/sd/2 https://insight.jci.org/articles/view/149870/sd/3 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Experimentelle und Klinische Pharmakologie und Toxikologie |
Professur: | M - Jun.-Prof. Dr. Daniela Yildiz |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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149870.1-20220120113113-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf | 8,44 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons