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Dissociation of native pentameric CRP (pCRP) into the monomeric structure (mCRP) liberates proinflammatory features, presumably contributing to excessive immune cell activation via unknown molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In a multi-translational study of systemic inflammation, we found a time- and inflammation-dependent pCRP dissociation into mCRP. We were able to confirm that mCRP co-localizes with leukocytes at the site of injury after polytrauma and therefore assessed whether the CRP conformation potentiates neutrophil activation. We found mCRP-induced neutrophil-extracellular trap formation in vitro and ex vivo involving nicotinamide adenine dinucleotide phosphate oxidase activation, p38\/mitogen-activated protein kinase signaling, and histone H3 citrullination. Mimicking the trauma milieu in a human ex vivo whole blood model, we found significant mCRP generation as well as NET formation, prevented by blocking pCRP conformational changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data provide novel molecular insights how CRP dissociation contributes to neutrophil activation as driver of various inflammatory disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12915-024-02093-8","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T10:45:22Z","timestamp":1736246722000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation"],"prefix":"10.1186","volume":"23","author":[{"given":"Ebru","family":"Karasu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Halbgebauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Sch\u00fctte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Greven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix M.","family":"Bl\u00e4sius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Zeller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Winninger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Braig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Alexander Christian","family":"Messerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Feuerstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Schultze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlheinz","family":"Peter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Knippschild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemens","family":"Horst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Hildebrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen U.","family":"Eisenhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2359-6516","authenticated-orcid":false,"given":"Markus","family":"Huber-Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"issue":"13","key":"2093_CR1","doi-asserted-by":"publisher","first-page":"866379","DOI":"10.3389\/fimmu.2022.866379","volume":"4","author":"M Slevin","year":"2022","unstructured":"Slevin M, Heidari N, Azamfirei L. 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