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It is known that hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) can limit neutrophil activation, but the respective mechanisms remain elusive. Here, we aimed to examine the underlying pathways in pulmonary inflammation. <jats:italic>In vivo<\/jats:italic>, C57BL\/6N mice received the H<jats:sub>2<\/jats:sub>S slow releasing compound GYY4137 prior to lipopolysaccharide (LPS) inhalation. LPS challenge led to pulmonary injury, inflammation, and neutrophil transmigration that were inhibited in response to H<jats:sub>2<\/jats:sub>S pretreatment. Moreover, H<jats:sub>2<\/jats:sub>S reduced mRNA expression of macrophage inflammatory protein-2 (MIP-2) and its receptor in lung tissue, as well as the accumulation of MIP-2 and interleukin-1\u03b2 in the alveolar space. <jats:italic>In vitro<\/jats:italic>, GYY4137 did not exert toxic effects on Hoxb8 neutrophils, but prevented their transmigration through an endothelial barrier in the presence and absence of MIP-2. In addition, the release of MIP-2 and reactive oxygen species from LPS-stimulated Hoxb8 neutrophils were directly inhibited by H<jats:sub>2<\/jats:sub>S. Taken together, we provide first evidence that H<jats:sub>2<\/jats:sub>S limits lung neutrophil sequestration upon LPS challenge. As proposed underlying mechanisms, H<jats:sub>2<\/jats:sub>S prevents neutrophil transmigration through the inflamed endothelium and directly inhibits pro-inflammatory as well as oxidative signalling in neutrophils. Subsequently, H<jats:sub>2<\/jats:sub>S pretreatment ameliorates LPS-induced ALI.<\/jats:p>","DOI":"10.1038\/s41598-018-33101-x","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T13:35:49Z","timestamp":1537968949000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative burst in lipopolysaccharide-induced acute lung injury"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5345-8523","authenticated-orcid":false,"given":"Simone","family":"Faller","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Hausler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Goeft","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc-Nicolas Andr\u00e9","family":"von Itter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Gyllenram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Hoetzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sashko G.","family":"Spassov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,10,2]]},"reference":[{"key":"33101_CR1","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1056\/NEJMoa022139","volume":"348","author":"GS Martin","year":"2003","unstructured":"Martin, G. 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