Academic Journal
A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation
| العنوان: | A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation |
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| المؤلفون: | Karasu, Ebru, Halbgebauer, Rebecca, Schütte, Lena M., Greven, Johannes, Bläsius, Felix M., Zeller, Johannes, Winninger, Oscar, Braig, David, Messerer, David Alexander Christian, Berger, Bettina, Feuerstein, Hendrik, Schultze, Anke, Peter, Karlheinz, Knippschild, Uwe, Horst, Klemens, Hildebrand, Frank, Eisenhardt, Steffen Ulrich, Huber-Lang, Markus |
| المصدر: | BMC biology. - 23, 1 (2025) , 4, ISSN: 1741-7007 |
| سنة النشر: | 2025 |
| المجموعة: | University of Freiburg: FreiDok |
| الوصف: | Background C-reactive protein (CRP) represents a routine diagnostic marker of inflammation. 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. Results 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. Conclusions Our data provide novel molecular insights how CRP dissociation contributes to neutrophil activation as driver of various inflammatory disorders. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | |
| اللغة: | English |
| Relation: | https://freidok.uni-freiburg.de/data/262110 |
| DOI: | 10.1186/s12915-024-02093-8 |
| الاتاحة: | https://freidok.uni-freiburg.de/data/262110 https://nbn-resolving.org/urn:nbn:de:bsz:25-freidok-2621101 https://doi.org/10.1186/s12915-024-02093-8 https://freidok.uni-freiburg.de/dnb/download/262110 |
| Rights: | free |
| رقم الانضمام: | edsbas.D24F30BA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12915-024-02093-8 |
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