Some of these cytokines also have direct angiogenic effects. Macrophages produce several factors, other than proteases, that induce migration of endothelial cells. Most of them also support other stages of the angiogenic process such as mitosis or differentiation of endothelial cells. Their migratory effects are sufficient for initial neovascularization as migrating endothelial cells can form sprouts without proliferating. Angiogenin , another well-characterized nonmitogenic angiogenic factor does not appear to be released by macrophages.
Macrophages secrete or produce several factors that induce mitoses of capillary endothelium.
Basic FGF stimulates directed migration and proliferation of cultured endothelial cells and promotes formation of differentiated capillary tubes in vitro. These effects are associated with selective up-regulation of integrins on endothelial cells and induction of protease such as plasminogen activator. Direct angiogenic effects of PDGF are not unequivocal. Controversial effects of PDGF on endothelial cells may derive from the heterogeneity of endothelial cells. Apart from its direct effects on endothelium, PDGF has effects on other cells involved in wound healing.