Macrophages kill capillary cells in G(1) phase of the cell cycle during programmed vascular regression

Programmed capillary regression occurs during normal development of the eye and serves as a useful model for assessing the forces that drive vascular involution, Using a combination of S-phase labeling and liposome-mediated m acrophage elimination, we show that during regression, macrophages induce a poptosis of both pericytes and endothelial cells in a cell cycle stage-depe ndent manner, Target cells are signaled to die by macrophages approximately 15 hours after S-phase labeling and this corresponds to a point in mid-G(1 ) phase of the cell cycle. The tight correlation between the restriction po int of the cell cycle and the point where the macrophage death signal is re ceived suggests that the mitogen, matrix and cytoskeletal signals essential for cell-cycle progression may be inhibited by macrophages as a means of i nducing cell death. Furthermore, these experiments show that cells from two distinct lineages are induced to die as a consequence of macrophage action , and this provides evidence that macrophage-induced cell death may be a ge neral phenomenon during development and homeostasis.