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The crucial role of macrophages in lymphangiogenesis
Dontscho Kerjaschki
Dontscho Kerjaschki
Published September 1, 2005
Citation Information: J Clin Invest. 2005;115(9):2316-2319. https://doi.org/10.1172/JCI26354.
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The crucial role of macrophages in lymphangiogenesis

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Abstract

Lymphangiogenesis is associated with pathological processes such as the metastatic spread of carcinoma cells and organization of immunologically active lymphocytic infiltrates following organ transplantation. It has not yet been established whether expansion of the lymphatic vascular meshwork is driven by incorporation of progenitor cells or by local endothelial cell division. In this issue of the JCI, Maruyama et al. provide evidence that after mouse corneal transplant, CD11b+ macrophages infiltrate the corneal stroma and transdifferentiate into lymphatic endothelial cell clusters that join existing lymphatic vessels. In complementary in vitro experiments, murine peritoneal macrophages expressed lymphatic endothelial markers and formed vessel-like protrusions. These findings add yet another facet to the plasticity of macrophages, which are already known to transform from naive monocytes into VEGF-C–producing cells. Thus, macrophages support lymphangiogenesis in 2 different ways, either by transdifferentiating and directly incorporating into the endothelial layer or by stimulating division of preexistent local lymphatic endothelial cells.

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Dontscho Kerjaschki

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Figure 1

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Lymphangiogenesis: a split path for monocytes/macrophages. A subfraction...
Lymphangiogenesis: a split path for monocytes/macrophages. A subfraction of naive blood-borne monocytes constitutively express VEGFR-3 on their surface. It has been proposed that these monocytes emigrate from blood vessels and then follow 2 different pathways. Pathway A (green arrows): Monocytes are exposed to TNF-α and/or other proinflammatory agents in the (peritumoral) stroma and are converted into VEGF-C_ secreting macrophages that presumably induce proliferation of lymphatic endothelial cells. Pathway B (red arrows): In this issue of the JCI, Maruyama et al. (10) describe how, in a mouse corneal transplant model, macrophages transdifferentiate into lymphatic endothelial cells by forming cell aggregates and vesicles that integrate into an existing lymphatic vessel.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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