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Using phage display, a Designed-Ankyrin-Repeat-Protein (DARPin) was selected as a novel binding protein targeting and blocking the \u03b1<jats:sub>M<\/jats:sub>I-domain, an activation-specific epitope of Mac-1. This DARPin, named F7, specifically binds to activated Mac-1 on mouse and human monocytes as determined by flow cytometry. Homology modelling and docking studies defined distinct interaction sites which were verified by mutagenesis. Intravital microscopy showed reduced leukocyte\u2013endothelium adhesion in mice treated with this DARPin. Using mouse models of sepsis, myocarditis and ischaemia\/reperfusion injury, we demonstrate therapeutic anti-inflammatory effects. Finally, the activated Mac-1-specific DARPin is established as a tool to detect monocyte activation in patients receiving extra-corporeal membrane oxygenation, as well as suffering from sepsis and ST-elevation myocardial infarction. 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Eur Heart J 39:111\u2013116. https:\/\/doi.org\/10.1093\/eurheartj\/ehx218","journal-title":"Eur Heart J"}],"container-title":["Basic Research in Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00395-021-00849-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00395-021-00849-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00395-021-00849-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:16:23Z","timestamp":1724631383000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00395-021-00849-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,15]]},"references-count":84,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["849"],"URL":"https:\/\/doi.org\/10.1007\/s00395-021-00849-9","relation":{},"ISSN":["0300-8428","1435-1803"],"issn-type":[{"value":"0300-8428","type":"print"},{"value":"1435-1803","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,15]]},"assertion":[{"value":"31 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"Experiments involving human or animal samples were approved by the institutional review board of the University of Freiburg, Germany, and the Alfred Hospital, Melbourne, Australia. Participants or their legal representatives (in the case of ECMO patients) gave written informed consent in accordance with the Declaration of Helsinki. Both observational studies were registered in the German Clinical Trials Register: DRKS00005277 (STEMI-patients), DRKS00011106 (ECMO patients).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All patients or their legal representatives provided informed consent prior to inclusion into the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"This manuscript does not include any pictures of patients and is not a case report. The presentation of data in this manuscript do not allow the identification of study participants. All patients or their legal representatives provided informed consent prior to inclusion into the study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}],"article-number":"17"}}