Wnt signaling regulates transendothelial migration of monocytes.

The Wnt-signaling pathway plays a critical role in directing cell fate during embry- ogenesis. 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. Activa- tion of the Wnt/-catenin pathway by LiCl or Wnt3a increased -catenin protein levels in mono- cytes but not in granulocytes. It is interesting that the activation of Wnt/-catenin signaling via Wnt3a in monocytes resulted in a decrease in migration through an endothelial layer (human dermal mi- crovascular endothelial cell-1). Further experi- ments revealed that the decrease in transendothe- lial migration was associated with specific mono- cyte 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 -catenin revealed a Wnt3a-induced increase of -catenin in the cyto- plasm. Wnt3a exposure did not result in any acti- vation of the classical Wnt-target gene c-myc or a Wnt-target gene involved in cell adhesion (Con- nexin43). Our study implicates for the first time a role of canonical Wnt signaling in inflammatory processes in monocytes. J. Leukoc. Biol. 79: 1306-1313; 2006.