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126. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

28.04. - 01.05.2009, München

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A causal role of C-reactive protein (CRP) in inflammation: Conformational rearrangement in CRP is required for enhanced pro-inflammatory leukocyte activation and leukocyte adhesion in ischemia-reperfusion of the striated muscle

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  • corresponding author S. U. Eisenhardt - Universitätsklinikum Freiburg, Abteilung für Plastische und Handchirurgie, Freiburg, Deutschland
  • A. Murphy - Baker Heart Research Institute, Melbourne, Australia
  • K.J. Woollard - Baker Heart Research Institute, Melbourne, Australia
  • A. Bobik - Baker Heart Research Institute, Melbourne, Australia
  • J. Chin-Dusting - Baker Heart Research Institute, Melbourne, Australia
  • K. Peter - Baker Heart Research Institute, Melbourne, Australia
  • G.B. Stark - Universitätsklinikum Freiburg, Abteilung für Plastische und Handchirurgie, Freiburg, Deutschland

Deutsche Gesellschaft für Chirurgie. 126. Kongress der Deutschen Gesellschaft für Chirurgie. München, 28.04.-01.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09dgch11009

doi: 10.3205/09dgch293, urn:nbn:de:0183-09dgch2937

Published: April 23, 2009

© 2009 Eisenhardt et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Introduction: C-reactive protein (CRP) is the prototypic acute phase reactant and consists of 5 identical non-covalently linked subunits. Recently it has been proposed that CRP is not only a marker, but also a mediator of inflammatory processes. Here we investigated the pathogenetic role of CRP in ischemia-reperfusion and the influence of the conformational change from pentameric CRP (pCRP) to its individual subunits (monomeric CRP: mCRP) on the pro-inflammatory effects of CRP.

Material and methods: We immunohistologically examined ischemically challenged and reperfused tissue of the free muscle flap. We examined the impact of native, pentameric CRP and mCRP on the activation of the monocyte integrin Mac-1 (CD11b/CD18), a key regulator of monocyte adhesion to endothelial cells in the microcirculation of inflamed tissues. We further investigated the effect of different CRP isoforms on monocyte adhesion to fibrinogen under static and to adherent platelets and human endothelial cells under shear flow conditions. Specific blockers were used to assess the signal transduction pathways involved in mediating pro-inflammatory CRP effects.

Results: We detect mCRP, but not pCRP deposition in reperfused, inflamed muscle tissue after free muscle transfer. In vitro low concentrations of mCRP(5μg/ml)lead to significantly increased monocyte adhesion to fibrinogen, platelets and human endothelial cells under shear–flow conditions via Mac-1 activation through signal-transduction pathways involving PI3- and Src-kinases. pCRP does not exert pro-inflammatory properties in physiological concentrations.

Conclusion: In conclusion, these results suggest that loss of the pentameric symmetry in CRP, resulting in formation of mCRP, enhances its pro-inflammatory properties. The deposition of mCRP in ischemia-reperfusion injury suggests a causal role in the pro-inflammatory pathology of ischemia-reperfusion and associated microcirculatory alterations. Furthermore, our results might explain previously published opposing results regarding the pro-inflammatory properties of CRP and identify mCRP as a potential therapeutic target in inflammatory diseases.