Evidence map›Paper›PMID 39773175›Full record

ArticleBMC biology2025

A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation.

Ebru Karasu, Rebecca Halbgebauer, Lena Schütte, Johannes Greven, Felix M Bläsius, Johannes Zeller, Oscar Winninger, David Braig, David Alexander Christian Messerer, Bettina Berger and 8 more

Abstract read
In one paragraph

Article in BMC biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Ebru Karasu *Institute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
Rebecca Halbgebauer *Institute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
Lena SchütteInstitute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
Johannes GrevenDepartment of Orthopedic Trauma Surgery, RWTH Aachen University, Aachen, Germany.
Felix M BläsiusDepartment of Orthopedic Trauma Surgery, RWTH Aachen University, Aachen, Germany.
Johannes ZellerDepartment of Plastic and Hand Surgery, Medical Faculty of the University of Freiburg, University of Freiburg Medical Centre Freiburg, Freiburg, Germany.
Oscar WinningerDepartment of Plastic and Hand Surgery, Medical Faculty of the University of Freiburg, University of Freiburg Medical Centre Freiburg, Freiburg, Germany.
David BraigDepartment of Plastic and Hand Surgery, Medical Faculty of the University of Freiburg, University of Freiburg Medical Centre Freiburg, Freiburg, Germany.
David Alexander Christian MessererInstitute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
Bettina BergerInstitute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
Hendrik FeuersteinInstitute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
Anke SchultzeInstitute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
Karlheinz PeterBaker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Australia.
Uwe KnippschildDepartment of General and Visceral Surgery, Ulm University Medical Center, 89081, Ulm, Germany.
Klemens HorstDepartment of Orthopedic Trauma Surgery, RWTH Aachen University, Aachen, Germany.
Frank HildebrandDepartment of Orthopedic Trauma Surgery, RWTH Aachen University, Aachen, Germany.
Steffen U Eisenhardt *Department of Plastic and Hand Surgery, Medical Faculty of the University of Freiburg, University of Freiburg Medical Centre Freiburg, Freiburg, Germany.
Markus Huber-Lang *Institute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Helmholtzstrasse 8/1, 89081, Ulm, Germany. markus.huber-lang@uniklinik-ulm.de.ORCID 0000-0003-2359-6516

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundC-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.

resultsIn 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.

conclusionsOur data provide novel molecular insights how CRP dissociation contributes to neutrophil activation as driver of various inflammatory disorders.

Indexed as

C-Reactive ProteinExtracellular TrapsInflammationNeutrophilsProtein ConformationHumansMaleNeutrophil ActivationC-Reactive ProteinC-reactive-protein (CRP)InflammationMonomeric CRP (mCRP)Neutrophil activationNeutrophil extracellular trap (NET)Polytrauma (PT)Severe injury

Identifiers

PMID39773175
PMCPMC11708171

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.