MACROPHAGE-DERIVED ANGIOGENESIS FACTORS

A majority of angiogenic factors has been shown to be produced by macrophages. This review will give a concise description of their biochemical nature, their isolation from macrophages and their angiogenic activity. Among the factors with mitogenic effects on endothelial cells are basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF-alpha) and very probably insulin-like growth factor-1 (IGF-1). Other secretory products such as angiotropin and human angiogenic factor (HAF) are nonmitogenic but promote angiogenesis by inducing migration of endothelial cells. Prostaglandins, platelet-derived growth factor (PDGF), granulocyte-macrophage- and granulocyte-colony stimulating factor (GM-CSF, G-CSF), interleukin 6 (IL-6) and angiotensin converting enzyme (ACE) have also been shown to be angiogenic, but their mode of action is still to be clearly defined. As the extracellular matrix appears to be involved in the control of angiogenesis, macrophage-derived factors that can alter this structure via degradation or via the clotting system will also be discussed. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1) and transforming growth factor-beta (TGF-beta) have complex actions on endothelial cells, and can partially inhibit angiogenesis. Among the factors which solely inhibit neovascularization are the interferons. As it is not known whether all of these factors play a role in angiogenesis in vivo attempts to detect them in situ during the course of neovascularization will be described. Finally macrophages will be discussed as cells that may not be mandatory for each phase of the angiogenic process but whose angiogenic capabilities are comprehensive and unsurpassed by any other cell.