{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:33:38Z","timestamp":1790886818850,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T00:00:00Z","timestamp":1642896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DR1013\/1-1"],"award-info":[{"award-number":["DR1013\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HIPS-UdS TANDEM initiative","award":["Project 1"],"award-info":[{"award-number":["Project 1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pneumonia is a life-threatening disease often caused by infection with Streptococcus pneumoniae and Pseudomonas aeruginosa. Many of the mediators (e.g., TNF, IL-6R) and junction molecules (e.g., E-cadherin) orchestrating inflammatory cell recruitment and loss of barrier integrity are proteolytically cleaved through a disintegrin and metalloproteinases (ADAMs). We could show by Western blot, surface expression analysis and measurement of proteolytic activity in cell-based assays, that ADAM10 in epithelial cells is upregulated and activated upon infection with Pseudomonas aeruginosa and Exotoxin A (ExoA), but not upon infection with Streptococcus pneumoniae. Targeting ADAM10 by pharmacological inhibition or gene silencing, we demonstrated that this activation was critical for cleavage of E-cadherin and modulated permeability and epithelial integrity. Stimulation with heat-inactivated bacteria revealed that the activation was based on the toxin repertoire rather than the interaction with the bacterial particle itself. Furthermore, calcium imaging experiments showed that the ExoA action was based on the induction of calcium influx. Investigating the extracellular vesicles and their proteolytic activity, we could show that Pseudomonas aeruginosa triggered exosomal release of ADAM10 and proteolytic cleavage in trans. This newly described mechanism could constitute an essential mechanism causing systemic inflammation in patients suffering from Pseudomonas aeruginosa-induced pneumonia stimulating future translational studies.<\/jats:p>","DOI":"10.3390\/ijms23031259","type":"journal-article","created":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T20:32:52Z","timestamp":1642969972000},"page":"1259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Pseudomonas aeruginosa Triggered Exosomal Release of ADAM10 Mediates Proteolytic Cleavage in Trans"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-3583","authenticated-orcid":false,"given":"Ahmad","family":"Aljohmani","sequence":"first","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology, PZMS, ZHMB, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Opitz","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Respiratory Medicine, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Bischoff","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hygiene, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Yildiz","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology, PZMS, ZHMB, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ajic.2014.07.014","article-title":"A decade of investment in infection prevention: A cost-effectiveness analysis","volume":"43","author":"Dick","year":"2015","journal-title":"Am. 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