Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation
- Author(s)
- Gordon, EJ; Rao, S; Pollard, JW; Nutt, SL; Lang, RA; Harvey, NL;
- Details
- Publication Year 2010-11-15,Volume 137,Issue #22,Page 3899-3910
- Journal Title
- DEVELOPMENT
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- COMPANY OF BIOLOGISTS LTD
- Keywords
- MONONUCLEAR PHAGOCYTE SYSTEM; HYALURONAN RECEPTOR LYVE-1; GREEN FLUORESCENT PROTEIN; TRANSCRIPTION FACTOR PU.1; CD11B(+) MACROPHAGES; PROGENITOR CELLS; GROWTH-FACTOR; TIE2-EXPRESSING MONOCYTES; TARGETED DISRUPTION; TUMOR-CELLS
- Publisher's Version
- https://doi.org/10.1242/dev.050021
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2010-11-15 12:00:00