International Immunology Advance Access published online on April 24, 2006
International Immunology, doi:10.1093/intimm/dxl023
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1 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary; Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
* To whom correspondence should be addressed. The role of C-reactive protein (CRP) in atherosclerosis is controversial. It is not clear, either, if the presumed endothelium-activating effect of CRP resides in native CRP (nCRP) or in a conformational isoform of CRP known as modified CRP (mCRP). In the present study we evaluated and compared the effect of nCRP, recombinant modified CRP (rmCRP) and urea-modified CRP (umCRP) on human umbilical vein endothelial cells (HUVECs). CRP preparations were carefully analyzed by biochemical, immunological and cell biological methods in order to avoid endotoxin or sodium azide contamination as well as inappropriate conformational changes, which together had possibly been the main reason for the previously published controversial results. Neither nCRP nor mCRP showed significant cytotoxicity up to 100 µg ml-1 at 24 h but high concentrations of CRPs induced cell death at 48 h. rmCRP but not nCRP nor umCRP showed membrane binding to HUVEC by confocal microscopy. However, none of the CRP forms induced intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin expression or IL-8 production. Monocyte chemotactic protein-1 production was weakly inhibited by high concentration of both nCRP and rmCRP, analyzed by sandwich ELISA. Neither nCRP nor mCRP could induce pro-inflammatory changes in the phenotype of HUVECs. Therefore, our present findings do not support the notion that different isoforms of CRP alone have significant effects on inflammation of the vessel wall via an interaction with endothelial cells (ECs), although one cannot exclude the possibility that there may be significant differences among various types of ECs in the response to CRP.
Received August 9, 2005
Accepted March 10, 2006
Article
Proinflammatory changes in human umbilical cord vein endothelial cells can be induced neither by native nor by modified CRP
Melinda Oroszlán 1,
Eszter Herczenik 2,
Szabolcs Rugonfalvi-Kiss 3,
Anja Roos 4 *,
Alma J. Nauta 5,
Mohamed R. Daha 5,
Imre Gombos 6,
István Karádi 7,
László Romics 7,
Zoltán Prohászka 7,
George Füst 7,
and
László Cervenak 2
2 Research Group of Metabolism and Atherosclerosis, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary
3 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
4 Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands; Present address: Department of Clinical Chemistry, L2-27, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
5 Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
6 Department of Immunology, Lóránd Eötvös University, Budapest, Hungary
7 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary; Research Group of Metabolism and Atherosclerosis, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary
Anja Roos, E-mail: a.roos{at}lumc.nl
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