Figure 1.

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.