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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3158-3167. Prepublished online as a Blood First Edition Paper on July 11, 2007; DOI 10.1182/blood-2007-01-066811. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-01-066811v1 110/9/3158    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Halin, C. Articles by Detmar, M. Search for Related Content PubMed PubMed Citation Articles by Halin, C. Articles by Detmar, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY VEGF-A produced by chronically inflamed tissue induces lymphangiogenesis in draining lymph nodes Cornelia Halin1, Nadja E. Tobler1, Benjamin Vigl1, Lawrence F. Brown2, and Michael Detmar1 1 Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland; and 2 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA Lymphangiogenesis is involved in tumor cell metastasis and plays a major role in chronic inflammatory disorders. To investigate the role of lymphangiogenesis in inflammation, we induced and maintained delayed-type hypersensitivity (DTH) reactions in the ears of mice and then analyzed the resulting lymphangiogenesis in the inflamed tissue and draining lymph nodes (LNs) by quantitative fluorescence-activated cell sorting (FACS) and by immunofluorescence. Long-lasting inflammation induced a significant increase in the number of lymphatic endothelial cells, not only in the inflamed ears but also in the ear-draining auricular LNs. Inflammation-induced lymphangiogenesis was potently blocked by systemic administration of a vascular endothelial growth factor (VEGF)-A neutralizing antibody. Surprisingly, tissue inflammation specifically induced LN lymphangiogenesis but not LN angiogenesis. These findings were explained by analysis of both VEGF-A protein and mRNA levels, which revealed that VEGF-A was expressed at high mRNA and protein levels in inflamed ears but that expression was increased only at the protein level in activated LNs. Inflammation-induced lymphangiogenesis in LNs was independent of the presence of nodal B lymphocytes, as shown in B cell-deficient mice. Our data reveal that chronic inflammation actively induces lymphangiogenesis in LNs, which is controlled remotely, by lymphangiogenic factors produced at the site of inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Y. Lim, J. M. Rutkowski, J. Helft, S. T. Reddy, M. A. Swartz, G. J. Randolph, and V. Angeli Hypercholesterolemic Mice Exhibit Lymphatic Vessel Dysfunction and Degeneration Am. J. Pathol., September 1, 2009; 175(3): 1328 - 1337. [Abstract] [Full Text] [PDF] R. P. Kataru, K. Jung, C. Jang, H. 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