A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation
Abstract 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...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12915-024-02093-8 |
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| author | Ebru Karasu Rebecca Halbgebauer Lena Schütte Johannes Greven Felix M. Bläsius Johannes Zeller Oscar Winninger David Braig David Alexander Christian Messerer Bettina Berger Hendrik Feuerstein Anke Schultze Karlheinz Peter Uwe Knippschild Klemens Horst Frank Hildebrand Steffen U. Eisenhardt Markus Huber-Lang |
| author_facet | Ebru Karasu Rebecca Halbgebauer Lena Schütte Johannes Greven Felix M. Bläsius Johannes Zeller Oscar Winninger David Braig David Alexander Christian Messerer Bettina Berger Hendrik Feuerstein Anke Schultze Karlheinz Peter Uwe Knippschild Klemens Horst Frank Hildebrand Steffen U. Eisenhardt Markus Huber-Lang |
| author_sort | Ebru Karasu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-1f9a20d32bb04c878f258ff4d85ad9bf |
| institution | Kabale University |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj-art-1f9a20d32bb04c878f258ff4d85ad9bf2025-01-12T12:39:49ZengBMCBMC Biology1741-70072025-01-0123111710.1186/s12915-024-02093-8A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammationEbru Karasu0Rebecca Halbgebauer1Lena Schütte2Johannes Greven3Felix M. Bläsius4Johannes Zeller5Oscar Winninger6David Braig7David Alexander Christian Messerer8Bettina Berger9Hendrik Feuerstein10Anke Schultze11Karlheinz Peter12Uwe Knippschild13Klemens Horst14Frank Hildebrand15Steffen U. Eisenhardt16Markus Huber-Lang17Institute of Clinical and Experimental Trauma Immunology, University Hospital UlmInstitute of Clinical and Experimental Trauma Immunology, University Hospital UlmInstitute of Clinical and Experimental Trauma Immunology, University Hospital UlmDepartment of Orthopedic Trauma Surgery, RWTH Aachen UniversityDepartment of Orthopedic Trauma Surgery, RWTH Aachen UniversityDepartment of Plastic and Hand Surgery, Medical Faculty of the University of Freiburg, University of Freiburg Medical Centre FreiburgDepartment of Plastic and Hand Surgery, Medical Faculty of the University of Freiburg, University of Freiburg Medical Centre FreiburgDepartment of Plastic and Hand Surgery, Medical Faculty of the University of Freiburg, University of Freiburg Medical Centre FreiburgInstitute of Clinical and Experimental Trauma Immunology, University Hospital UlmInstitute of Clinical and Experimental Trauma Immunology, University Hospital UlmInstitute of Clinical and Experimental Trauma Immunology, University Hospital UlmInstitute of Clinical and Experimental Trauma Immunology, University Hospital UlmBaker Department of Cardiometabolic Health, University of MelbourneDepartment of General and Visceral Surgery, Ulm University Medical CenterDepartment of Orthopedic Trauma Surgery, RWTH Aachen UniversityDepartment of Orthopedic Trauma Surgery, RWTH Aachen UniversityDepartment of Plastic and Hand Surgery, Medical Faculty of the University of Freiburg, University of Freiburg Medical Centre FreiburgInstitute of Clinical and Experimental Trauma Immunology, University Hospital UlmAbstract 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.https://doi.org/10.1186/s12915-024-02093-8C-reactive-protein (CRP)Monomeric CRP (mCRP)Neutrophil activationNeutrophil extracellular trap (NET)InflammationSevere injury |
| spellingShingle | Ebru Karasu Rebecca Halbgebauer Lena Schütte Johannes Greven Felix M. Bläsius Johannes Zeller Oscar Winninger David Braig David Alexander Christian Messerer Bettina Berger Hendrik Feuerstein Anke Schultze Karlheinz Peter Uwe Knippschild Klemens Horst Frank Hildebrand Steffen U. Eisenhardt Markus Huber-Lang A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation BMC Biology C-reactive-protein (CRP) Monomeric CRP (mCRP) Neutrophil activation Neutrophil extracellular trap (NET) Inflammation Severe injury |
| title | A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation |
| title_full | A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation |
| title_fullStr | A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation |
| title_full_unstemmed | A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation |
| title_short | A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation |
| title_sort | conformational change of c reactive protein drives neutrophil extracellular trap formation in inflammation |
| topic | C-reactive-protein (CRP) Monomeric CRP (mCRP) Neutrophil activation Neutrophil extracellular trap (NET) Inflammation Severe injury |
| url | https://doi.org/10.1186/s12915-024-02093-8 |
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