Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Brueckmann, M. et al.

Brueckmann, Nahrup, Lang, Bertsch, Fukudome, Liebe, Kaden, Hoffmann, Borggrefe, Huhle,

Recombinant human activated protein C upregulates the release of soluble fractalkine from human endothelial cells.

Fractalkine is a unique endothelial cell-derived chemokine that functions both as a chemoattractant and as an adhesion molecule. Recent findings suggest that fractalkine plays an important role in inflammatory diseases by modulating leucocyte endothelial cell interactions. A modulating effect on the immune system in severe sepsis has been suggested for recombinant human activated protein C (rhAPC). However, a little is known about the effect of rhAPC on the endothelial release of soluble fractalkine. The effect of rhAPC (50 ng/ml to 10 microg/ml) and protein C (in equimolar concentrations) on the synthesis of fraktalkine-mRNA and release of soluble protein in human umbilical vein endothelial cells (HUVEC) was determined by reverse transcription-polymerase chain reaction and by an enzyme-linked immunosorbent assay. rhAPC at supra-pharmacological concentrations (1-10 microg/ml) stimulated fractalkine-messenger RNA-gene transcription and release of soluble fractalkine in a time- and dose-dependent manner, whereas the zymogen protein C was ineffective. As shown by experiments using monoclonal antibodies against the thrombin receptor, protease-activated receptor-1 ( PAR-1), PAR-2 and against the endothelial protein C receptor (EPCR), the effect of rhAPC on fractalkine upregulation was mediated by binding to the EPCR-receptor and signalling via PAR-1. These in vitro data demonstrate that induction of fractalkine release is an important response of HUVEC to stimulation with rhAPC and may lead to a better understanding of the molecular pathways involved in the mode of action of rhAPC. Further clinical trials are needed to confirm the in vivo relevance of these data.[1]

References

Recombinant human activated protein C upregulates the release of soluble fractalkine from human endothelial cells. Brueckmann, M., Nahrup, A.S., Lang, S., Bertsch, T., Fukudome, K., Liebe, V., Kaden, J.J., Hoffmann, U., Borggrefe, M., Huhle, G. Br. J. Haematol. (2006) [Pubmed]

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