Unbound MEDLINE

Promotion of lymphatic integrity by angiopoietin-1/Tie2 signaling during inflammation.

Abstract

The cutaneous lymphatic system plays a major role in tissue fluid homeostasis and inflammation of the skin. Although several lymphangiogenic factors are known to be involved in the formation of lymphatic vessels, the molecular mechanisms that maintain lymphatic integrity and control the functional drainage of interstitial fluid and resolution of inflammation remain unknown. Here we show that angiopoietin-1 (Ang1) enhances lymphatic integrity and function during inflammation. Ang1 transgenic mice under the control of keratin-14 (K14-Ang1) showed attenuated edema formation and inflammation after UV B (UVB) exposure. After UVB irradiation, blood vascular permeability was inhibited in K14-Ang1 mice compared with wild-type (WT) mice. Moreover, lymphatic vessels of WT mice were markedly enlarged and leaky in inflamed skin, whereas K14-Ang1 mice showed relatively contracted lymphatic vessels together with enhanced lymphatic vascularization. Expression of endothelial-specific tight junction molecules claudin-5 and zonula occludens protein 1 (ZO-1) was strongly down-regulated in the inflamed lymphatic vessels of UVB-exposed WT mice, whereas down-regulation of both claudin-5 and ZO-1 was blocked in UVB-exposed K14-Ang1 mice. In vitro studies revealed that the stability of lymphatic endothelial cells was enhanced in the presence of Ang1, presumably via up-regulation of claudin-5, as well as ZO-1. Claudin-5 knockdown markedly increased the permeability of lymphatic endothelial cells. Overall, our data strongly support the idea that Ang1/Tie2 signaling promotes lymphatic integrity by modulating tight junction molecule expression during inflammation.

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  • Publisher Full Text

    • Authors

    Kajiya K, Kidoya H, Sawane M, Matsumoto-Okazaki Y, Yamanishi H, Furuse M, Takakura N

    Institution

    Shiseido Innovative Science Research Center, Yokohama, Japan. kentaro.kajiya@to.shiseido.co.jp

    Source

    The American journal of pathology 180:3 2012 Mar pg 1273-82

    MeSH

    Angiopoietin-1
    Animals
    Cell Movement
    Claudins
    Edema
    Endothelial Cells
    Female
    Lymphangitis
    Lymphatic Vessels
    Mice
    Mice, Transgenic
    Otitis Externa
    RNA, Small Interfering
    Receptor, TIE-2
    Signal Transduction
    Tight Junctions
    Ultraviolet Rays

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    22200616