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Published online before print March 24, 2006

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(Journal of Leukocyte Biology. 2006;79:1306-1313.)
© 2006 by Society for Leukocyte Biology

Wnt signaling regulates transendothelial migration of monocytes

Lara Tickenbrock^*, Joachim Schwäble^*, Anke Strey, Bülent Sargin^*, Sina Hehn^*, Marion Baas^*, Chunaram Choudhary^*, Volker Gerke, Wolfgang E. Berdel^*, Carsten Müller-Tidow^*, and Hubert Serve^*,,1

^* Department of Medicine, Hematology and Oncology, Division of Hematology/Oncology,
Institute of Medical Biochemistry, ZMBE, and
The Interdisciplinary Centre of Clinical Research Münster (IZKF), University of Münster, Germany

¹Correspondence: Department of Medicine, Hematology and Oncology, University of Münster, Domagkstr. 3, 48129 Münster, Germany. E-mail: serve{at}uni-muenster.de

The Wnt-signaling pathway plays a critical role in directing cell fate during embryogenesis. Several lines of evidence also suggest a role in inflammatory processes. Here, we analyzed whether Wnt signaling plays a role in leukocyte inflammatory responses. Monocytes from healthy donors expressed different Frizzled receptors, which are ligands for the Wnt molecules. Activation of the Wnt/ß-catenin pathway by LiCl or Wnt3a increased ß-catenin protein levels in monocytes but not in granulocytes. It is interesting that the activation of Wnt/ß-catenin signaling via Wnt3a in monocytes resulted in a decrease in migration through an endothelial layer (human dermal microvascular endothelial cell-1). Further experiments revealed that the decrease in transendothelial migration was associated with specific monocyte adherence to endothelial cells after Wnt exposure. The specificity was verified by a lack of Wnt3a-induced adhesion to fibronectin, laminin, or collagen compared with endothelial interaction. Analysis of the distribution of ß-catenin revealed a Wnt3a-induced increase of ß-catenin in the cytoplasm. Wnt3a exposure did not result in any activation of the classical Wnt-target gene c-myc or a Wnt-target gene involved in cell adhesion (Connexin43). Our study implicates for the first time a role of canonical Wnt signaling in inflammatory processes in monocytes.

Key Words: ß-catenin • adhesion • inflammation

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