Figure 1. Schematic diagram depicting IAL observed during the acute phase of inflammation.

Upon activation by inflammatory stimuli, a local sprouting at the preexisting lymphatic vessels actively occurs in response to macrophage-secreted VEGF. As a result the lymphatic network grows and expands. During this process the VEGF-C/VEGFR-3 and VEGF-A/VEGF-R2 signaling pathways are known to have profound importance, yet other signaling pathways also seem to be involved. It has been suggested that lymphangiogenic macrophages can become incorporated into the lymphatic vessels and transdifferentiate into LECs, but this hypothesis requires more validation.