Figure 2

A model depicting the roles of macrophages in lymphangiogenesis. Macrophages have been proposed to contribute to lymphangiogenesis by acting as a source of lymphatic endothelial progenitor cells which incorporate into growing vessels, or by providing growth and patterning signals such as VEGF-A and VEGF-C/D, that stimulate the growth and/or function of the lymphatic vasculature. Lineage tracing studies have suggested that macrophages do not act as lymphatic endothelial progenitor cells, yet they share a close spatial localization with lymphatic vessels during development and express the lymphatic marker LYVE-1. These macrophages may assume localization in the walls of lymphatic vessels in order to perform an immune surveillance role, or be transiting through the lymphatic endothelium. Tumor associated macrophages (TAMs) and Tie2-expressing monocytes (TEMs) promote lymphangiogenesis by liberating proteases important for growth factor activation/matrix remodeling, producing chemokines that degrade the surrounding extracellular matrix (ECM), and recruiting additional inflammatory cells.