The lymphatic vasculature in disease

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Blood vessels form a closed circulatory system, whereas lymphatic vessels form a one-way conduit for tissue fluid and leukocytes. In most vertebrates, the main function of lymphatic vessels is to collect excess protein-rich fluid that has extravasated from blood vessels and transport it back into the blood circulation. Lymphatic vessels have an important immune surveillance function, as they import various antigens and activated antigen-presenting cells into the lymph nodes and export immune effector cells and humoral response factors into the blood circulation. Defects in lymphatic function can lead to lymph accumulation in tissues, dampened immune responses, connective tissue and fat accumulation, and tissue swelling known as lymphedema. This review highlights the most recent developments in lymphatic biology and how the lymphatic system contributes to the pathogenesis of various diseases involving immune and inflammatory responses and its role in disseminating tumor cells.

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Figure 1: The lymphatic vasculature and molecular mechanisms involved in its development and growth.
Figure 2: Lymphangiogenic growth factor–endothelial receptor interactions and binding sites of blocking antibodies.
Figure 3: A schematic model of lymphatic vessel function in organ transplantation.
Figure 4: Inhibitors of VEGF, VEGF-C, Ang2 and their receptors.
Figure 5: Mechanisms contributing to lymphatic metastasis.


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I am grateful to M. Bry, L. Eklund, S. Jalkanen, D. Kerjaschki, G.Y. Koh, V.-M. Leppänen, T. Mäkinen, A. Nykänen, M. Öhman, P. Ojala, P. Saharinen, M. Swartz and T. Tammela for useful discussions of the topics of this review. The lymph node images in Figure 5a were kindly provided by D. Kerjaschki and by G.Y. Koh, and draft figures were produced by H. Schmidt. The studies in my laboratory are currently supported by the Academy of Finland, the Finnish Cancer Organisations, the Association for International Cancer Research, the Sigrid Juselius Foundation, Seventh Framework Program of the European Union (ERC Advanced Grant), Finnish Foundation for Cardiovascular Research and Biocentrum Finland. I apologize to the many authors whose important work could not be cited because of space restrictions and the focus on the recent developments; older references appear in the many excellent reviews that have been cited.

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Correspondence to Kari Alitalo.

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K.A. is chairman of the Scientific Advisory Board of Circadian Technologies Limited. K.A. is also a consultant for Laurantis Pharma Oy.

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