The Journal of Experimental Medicine
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Published online 17 September 2001. doi:10.1084/jem.194.6.797
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© The Rockefeller University Press, 0022-1007/2001/9/797/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 6, September 17, 2001 797-808

Original Article

Isolation and Characterization of Dermal Lymphatic and Blood Endothelial Cells Reveal Stable and Functionally Specialized Cell Lineages

Ernst Kriehubera, Silvana Breiteneder-Geleffb, Marion Groegerc, Afschin Soleimanb, Sebastian F. Schoppmannb, Georg Stingla, Dontscho Kerjaschkib,e, and Dieter Maurera,d

a Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology,
b Department of Pathology, University of Vienna Medical School, Allgemeines Krankenhaus, A-1090 Vienna, Austria
c Division of General Dermatology, University of Vienna Medical School, Allgemeines Krankenhaus, A-1090 Vienna, Austria
d Center of Molecular Medicine of the Austrian Academy of Sciences, A-1090 Vienna, Austria
e Center of Excellence for Clinical and Experimental Oncology, AUH-Vienna, A-1090 Vienna, Austria
Department of Pathology, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.43-1-40400 519343-1-40400-5176

Dontscho.Kerjaschki{at}akh-wien.ac.at

A plexus of lymphatic vessels guides interstitial fluid, passenger leukocytes, and tumor cells toward regional lymph nodes. Microvascular endothelial cells (ECs) of lymph channels (LECs) are difficult to distinguish from those of blood vessels (BECs) because both express a similar set of markers, such as CD31, CD34, podocalyxin, von Willebrand factor (vWF), etc. Analysis of the specific properties of LECs was hampered so far by lack of tools to isolate LECs. Recently, the 38-kD mucoprotein podoplanin was found to be expressed by microvascular LECs but not BECs in vivo. Here we isolated for the first time podoplanin+ LECs and podoplanin– BECs from dermal cell suspensions by multicolor flow cytometry. Both EC types were propagated and stably expressed VE-cadherin, CD31, and vWF. Molecules selectively displayed by LECs in vivo, i.e., podoplanin, the hyaluronate receptor LYVE-1, and the vascular endothelial cell growth factor (VEGF)-C receptor, fms-like tyrosine kinase 4 (Flt-4)/VEGFR-3, were strongly expressed by expanded LECs, but not BECs. Conversely, BECs but not LECs expressed VEGF-C. LECs as well as BECs formed junctional contacts with similar molecular composition and ultrastructural features. Nevertheless, the two EC types assembled in vitro in vascular tubes in a strictly homotypic fashion. This EC specialization extends to the secretion of biologically relevant chemotactic factors: LECs, but not BECs, constitutively secrete the CC chemokine receptor (CCR)7 ligand secondary lymphoid tissue chemokine (SLC)/CCL21 at their basal side, while both subsets, upon activation, release macrophage inflammatory protein (MIP)-3{alpha}/CCL20 apically. These results demonstrate that LECs and BECs constitute stable and specialized EC lineages equipped with the potential to navigate leukocytes and, perhaps also, tumor cells into and out of the tissues.

Key Words: endothelial cell lineages • podoplanin • endothelial cell tube formation • vascular endothelial cell growth factors • chemokines

Abbreviations used in this paper: BEC, blood vessel EC; CCR, CC chemokine receptor; DC, dendritic cell; EC, endothelial cell; Flt-4, fms-like tyrosine kinase 4; LEC, lymphatic EC; MIP, macrophage inflammatory protein; nt, nucleotide(s); PFA, paraformaldehyde; SLC, secondary lymphoid tissue chemokine; UEA I, Ulex europeaus agglutinin I; VEGF, vascular endothelial cell growth factor; vWF, von Willebrand factor; WP, Weibel-Palade.

E. Kriehuber and S. Breiteneder-Geleff contributed equally to this work.

© 2001 The Rockefeller University Press


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