Regulation of Angiogenesis by Macrophages, Dendritic Cells, and Circulating Myelomonocytic Cells

Angiogenesis during reactive and pathologic processes is characteristically associated with inflammation. Macrophages and dendritic cells present in the inflammatory infiltrate contribute to the angiogenic process by multiple mechanisms. Macrophages produce a broad array of angiogenic growth factors and cytokines, generate conduits for blood flow through proteolytic mechanisms, and promote the remodeling of arterioles into arteries. They can also inhibit angiogenesis and cause reabsorption of neovessels by inducing endothelial cell death. Dendritic cells can stimulate or inhibit angiogenesis depending on their activation status and subset specificity. Dendritic cells stimulate angiogenesis by secreting angiogenic factors and cytokines, promoting the proangiogenic activity of T lymphocytes, and trans-differentiating into endothelial cells. Inflammatory infiltrates associated with angiogenesis also contain Tie2+, VEGFR2+, and GR1+ myelomonocytic cells which actively regulate the angiogenic process through paracrine mechanisms. In this paper we review our current knowledge of this field and discuss how recent advances have provided the rationale for novel therapeutic approaches against cancer.