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Mediators of Inflammation
Volume 2013, Article ID 279781, 11 pages
Research Article

The Endothelial Tyrosine Phosphatase SHP-1 Plays an Important Role for Vascular Haemostasis in TNFα-Induced Inflammation In Vivo

1Medizinische Klinik und Poliklinik IV, Innenstadt, Ludwig Maximilians Universität München, Ziemssenstr. 1, 80336 Munich, Germany
2Walter Brendel Zentrum für Experimentelle Medizin, Ludwig Maximilians Universität München, Marchioninistr. 27, 81377 Munich, Germany
3Frauenklinik und Poliklinik der Technischen Universität München, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany
4Invasive Kardiologie, Klinikum Starnberg, Oßwaldstr. 1, 82319 Starnberg, Germany

Received 21 December 2012; Revised 6 March 2013; Accepted 25 March 2013

Academic Editor: Austin Meng Guo

Copyright © 2013 Elisabeth Koch et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Introduction. Inflammation and endothelium-derived superoxides are important pathomechanisms in atherothrombotic diseases. We could previously show that the tyrosine phosphatase SHP-1 acts as a negative regulator in endothelial superoxide production. In this study we investigated the influence of SHP-1 on platelet-endothelium interaction and arterial thrombosis in TNFα-induced endothelial inflammation in vivo. Methods. Arteriolar thrombosis and platelet rolling in vivo were investigated in C57BL/6 mice using intravital microscopy in the dorsal skinfold chamber microcirculation model. Results. Inhibition of SHP-1 by the specific pharmacological inhibitor sodium stibogluconate did not significantly enhance platelet-endothelium interaction in vivo under physiological conditions but led to an augmented fraction of rolling platelets in TNFα-induced systemic inflammation. Accordingly, ferric-chloride-induced arteriolar thrombus formation, which was already increased by SHP-1 inhibition, was further enhanced in the setting of TNFα-induced inflammation. Platelet aggregation in vitro as well as ex vivo was not influenced by SHP-1-inhibition. In cultured endothelial cells, sodium stibogluconate increased TNFα-induced surface expression of p-selectin and von Willebrand factor. Additionally, TNFα increased SHP-1 activity and protein expression. Conclusions. The endothelial tyrosine phosphatase SHP-1 plays an important role for vascular hemostasis in vivo, which is crucial in TNFα-induced endothelial inflammation where it may serve as an autoinhibitory molecule to prevent excess inflammatory response and thrombus formation.