Published online before print September 4, 2008

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(American Journal of Pathology. 2008;173:1202-1209.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.080101

Lymphatic Precollectors Contain a Novel, Specialized Subpopulation of Podoplanin^low, CCL27-Expressing Lymphatic Endothelial Cells

Nikolaus Wick^*, Daniela Haluza^*, Elisabeth Gurnhofer^*, Ingrid Raab^*, Marie-Theres Kasimir, Michael Prinz, Carl-Walter Steiner, Christina Reinisch^¶, Anny Howorka^*, Pietro Giovanoli^||**, Sabine Buchsbaum^||, Sigurd Krieger^*, Erwin Tschachler^¶, Peter Petzelbauer and Dontscho Kerjaschki^*

From the Department of Pathology;^* the Department of Surgery, Division of Cardiac-Thoracic Surgery; the Core Unit for Medical Statistics and Informatics; the Department of Internal Medicine, Division of Rheumatology; the Department of Dermatology,^¶ Research Unit of Biology and Pathobiology of Human Skin; the Department of Surgery,|| Division of Plastic and Reconstructive Surgery; and the Department of Dermatology, Division of General Dermatology, Vienna Medical University, Vienna, Austria; and the Department of Reconstructive Surgery,^** University Hospital Zurich, Zurich, Switzerland

Expression of the lymphoendothelial marker membrane mucoprotein podoplanin (podo) distinguishes endothelial cells of both blood and lymphatic lineages. We have previously discovered two distinct subpopulations of lymphatic endothelial cells (LECs) in human skin that were defined by their cell surface densities of podoplanin and were designated LEC^podo-low and LEC^podo-high. LEC^podo-low is restricted to lymphatic precollector vessels that originate from initial LEC^podo-high-containing lymphatic capillaries and selectively express several pro-inflammatory factors. In addition to the chemokine receptor protein Duffy blood group antigen receptor for chemokines, these factors include the constitutively expressed chemokine CCL27, which is responsible for the accumulation of pathogenic CCR10⁺ T lymphocytes in human inflammatory skin diseases. In this study, we report that CCR10⁺ T cells accumulate preferentially both around and within CCL27⁺ LEC^podo-low precollector vessels in skin biopsies of human inflammatory disease. In transmigration assays, isolated CCR10⁺ T lymphocytes are chemotactically attracted by LEC^podo-low in a CCL27-dependent fashion, but not by LEC^podo-high. These observations indicate that LEC^podo-low-containing precollector vessels constitute a specialized segment of the initial lymphatic microvasculature, and we hypothesize that these LEC^podo-low-containing vessels are involved in the trafficking of CCR10⁺ T cells during skin inflammation.