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首页> 外文期刊>Development >Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation.
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Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation.

机译：巨噬细胞通过调节淋巴管内皮细胞增殖来定义发育过程中的真皮淋巴管口径。

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Macrophages have been suggested to stimulate neo-lymphangiogenesis in settings of inflammation via two potential mechanisms: (1) acting as a source of lymphatic endothelial progenitor cells via the ability to transdifferentiate into lymphatic endothelial cells and be incorporated into growing lymphatic vessels; and (2) providing a crucial source of pro-lymphangiogenic growth factors and proteases. We set out to establish whether cells of the myeloid lineage are important for development of the lymphatic vasculature through either of these mechanisms. Here, we provide lineage tracing evidence to demonstrate that lymphatic endothelial cells arise independently of the myeloid lineage during both embryogenesis and tumour-stimulated lymphangiogenesis in the mouse, thus excluding macrophages as a source of lymphatic endothelial progenitor cells in these settings. In addition, we demonstrate that the dermal lymphatic vasculature of PU.1(-/-) and Csf1r(-/-) macrophage-deficient mouse embryos is hyperplastic owing to elevated lymphatic endothelial cell proliferation, suggesting that cells of the myeloid lineage provide signals that act to restrain lymphatic vessel calibre in the skin during development. In contrast to what has been demonstrated in settings of inflammation, macrophages do not comprise the principal source of pro-lymphangiogenic growth factors, including VEGFC and VEGFD, in the embryonic dermal microenvironment, illustrating that the sources of patterning and proliferative signals driving embryonic and disease-stimulated lymphangiogenesis are likely to be distinct.
机译：已经提出巨噬细胞可通过两种潜在的机制刺激炎症环境中的新淋巴管生成：（1）通过转分化为淋巴内皮细胞并整合到生长的淋巴管中的能力，作为淋巴内皮祖细胞的来源; （2）提供促淋巴管生成的生长因子和蛋白酶的重要来源。我们着手通过这些机制中的任何一种来确定髓系谱系的细胞对于淋巴管系统的发育是否重要。在这里，我们提供了谱系追踪证据，以证明在小鼠胚胎发生和肿瘤刺激的淋巴血管生成过程中，淋巴管内皮细胞独立于髓系谱系而出现，因此在这些情况下不将巨噬细胞作为淋巴管内皮祖细胞的来源。此外，我们证明PU.1（-/-）和Csf1r（-/-）巨噬细胞缺陷型小鼠胚胎的真皮淋巴管系统是增生的，因为淋巴管内皮细胞增殖升高，这表明髓系的细胞提供信号在发育过程中起到抑制皮肤淋巴管口径的作用。与炎症环境中已证明的相反，巨噬细胞在胚胎真皮微环境中不构成促淋巴管生成生长因子的主要来源，包括VEGFC和VEGFD，这说明驱动胚胎和疾病的模式和增殖信号的来源刺激的淋巴管生成可能很明显。

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