Wnt signaling regulates transendothelial migration of monocytes.
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/beta-catenin pathway by LiCl or Wnt3a increased beta-catenin protein levels in monocytes but not in granulocytes. It is interesting that the activation of Wnt/beta-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 beta-catenin revealed a Wnt3a-induced increase of beta-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.
Department of Medicine, Hematology and Oncology, University of Münster, Domagkstr. 3, 48129 Münster, Germany.
Lara
L
Tickenbrock
Joachim
J
Schwäble
Anke
A
Strey
Bülent
B
Sargin
Sina
S
Hehn
Marion
M
Baas
Chunaram
C
Choudhary
Volker
V
Gerke
Wolfgang E
WE
Berdel
Carsten
C
Müller-Tidow
Hubert
H
Serve
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D004730:Endothelium, Vascular / Q000166:cytology*; D051157:Frizzled Receptors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D006098:Granulocytes / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D051157:Frizzled Receptors; D011993:Recombinant Fusion Proteins; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin; D018021:Lithium Chloride