Induction of neovascularization and nonlymphoid mesenchymal cell proliferation by macrophage cell lines

The mature murine macrophage-like cells NCTC-3749 and J-774, the immature human macrophage-like cells U-937-1, and their conditioned media exhibited potent angiogenic activity in rat corneas and stimulated proliferation of bovine aortic endothelial cells (BAEC) and DNA synthesis in BALB/c-3T3 cells in culture. In contrast, the immature human macrophage-like cells HL-60 and their conditioned media either failed to produce or release detectable quantities of these activities. Exposure of HL-60 cells to phorbol-myristate-acetate (PMA) did not enhance expression of angiogenic and growth stimulating activities by these cells. Both the angiogenic and growth stimulating activities appear to be mediated by a factor(s) that has biochemical properties in common with macrophage-derived growth factor (MDGF) produced by normal rat peritoneal macrophages. These results suggest that NCTC-3749, J-774, and U-937-1 macrophage-like cell lines may be a useful source for the large scale production and characterization of MDGF and macrophage-derived angiogenic activity.