title: Coxsackie- and adenovirus receptor (CAR) is expressed in lymphatic vessels in human skin and affects lymphatic endothelial cell function in vitro.
abstract: Lymphatic vessels play an important role in tissue fluid homeostasis, intestinal fat absorption and immunosurveillance. Furthermore, they are involved in pathologic conditions, such as tumor cell metastasis and chronic inflammation. In comparison to blood vessels, the molecular phenotype of lymphatic vessels is less well characterized. Performing comparative gene expression analysis we have recently found that coxsackie- and adenovirus receptor (CAR) is significantly more highly expressed in cultured human, skin-derived lymphatic endothelial cells (LECs), as compared to blood vascular endothelial cells. Here, we have confirmed these results at the protein level, using Western blot and FACS analysis. Immunofluorescence performed on human skin confirmed that CAR is expressed at detectable levels in lymphatic vessels, but not in blood vessels. To address the functional significance of CAR expression, we modulated CAR expression levels in cultured LECs in vitro by siRNA- and vector-based transfection approaches. Functional assays performed with the transfected cells revealed that CAR is involved in distinct cellular processes in LECs, such as cell adhesion, migration, tube formation and the control of vascular permeability. In contrast, no effect of CAR on LEC proliferation was observed. Overall, our data suggest that CAR stabilizes LEC-LEC interactions in the skin and may contribute to lymphatic vessel integrity.
authors.affiliation: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Wolfgang-Pauli Str. 10, CH-8093 Zurich, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Vigl
authors.forename: Claudia
authors.initials: C
authors.lastname: Zgraggen
authors.forename: Nadia
authors.initials: N
authors.lastname: Rehman
authors.forename: Nadia E
authors.initials: NE
authors.lastname: Banziger-Tobler
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
authors.forename: Cornelia
authors.initials: C
authors.lastname: Halin
mesh_terms: D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003911:Dextrans / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D052816:Foreskin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism; D042601:Lymphatic Vessels / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D033921:Vesicular Transport Proteins / Q000235:genetics; D000098853:Podoplanin
chemical_list: D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D018799:Intercellular Adhesion Molecule-1; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D034741:RNA, Small Interfering; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; C568771:CLMP protein, human; C119248:LYVE1 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin; C015219:fluorescein isothiocyanate dextran