The role of macrophages in clearing programmed cell death in the developing kidney.

Abstract

The metanephric kidney develops from two tissue sources, the metanephric mesenchymal blastema and the ureteric bud epithelium. Following a complex interplay of inductive signals between these two tissues, small groups of metanephric mesenchymal cells aggregate and epithelialise to form young nephrons. As this is happening, significant numbers of cells in close proximity to the forming nephrons undergo programmed cell death or apoptosis. In this paper we investigate the clearance of developmental cell death in the mouse kidney between embryonic days 11.5 and 16.5; specifically, we address the issue of whether specialist macrophages or non-specialist neighbouring mesenchymal cells are responsible for phagocytosis and removal of dying cells. We show, using a monoclonal antibody F4/80 that specifically recognizes murine macrophages, that whenever and wherever there is cell death in the developing mesonephric or metanephric kidney there are also haemopoietically derived specialist macrophages. Moreover, in the mesonephros and from E14.5 in the metanephric kidney, we see large numbers of macrophages clearly swollen with phagocytosed apoptotic bodies. Double-labelling experiments using the DNA dye 7AAD to reveal condensed apoptotic nuclei and F4/80 to reveal macrophage plasma membranes show definitively that the majority of dying cells in the developing kidney are engulfed by macrophages.