Model for macrophage-derived Wnt5a regulation of angiogenesis. (A) A wound or inflammation induces secretion of cytokines, including the macrophage chemotactic cytokines M-CSF and CCL2, by fibroblasts, pericytes, EC and other stromal cells present at the site of injury. (B) Monocytes extravasate from the blood vessels and secrete Wnt5a, which upregulates expression of Tie2 in macrophages and EC (note: basal levels of Tie-2 expression not depicted) as well as induces proliferation and migration of sprouting EC. (C) EC and pericyte-derived Ang2 signals through Tie2 expressed on the surface of TEMs, further polarizing macrophages to a proangiogenic phenotype. (D) TEMs then participate in the maturation phases of angiogenesis, including vessel lumen formation and anastomosis.