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The role of macrophages in clearing programmed cell death in the developing kidney
1Department of Anatomy and Developmental Biology, University College London, UK. v.camp@ucl.ac.uk
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.
Insights
Specialist macrophages clear dying cells during mouse kidney development. These immune cells, identified by F4/80, engulf apoptotic bodies, ensuring proper nephron formation.
Area of Science:
- Developmental biology
- Immunology
- Renal physiology
Background:
- Kidney development involves complex cell-cell interactions and programmed cell death.
- The roles of different cell types in clearing apoptotic cells during kidney morphogenesis are not fully understood.
Purpose of the Study:
- To investigate the cellular mechanisms responsible for clearing apoptotic cells during mouse kidney development.
- To determine whether macrophages or neighboring mesenchymal cells phagocytose dying cells in the developing kidney.
Main Methods:
- Utilized a monoclonal antibody F4/80 to identify murine macrophages.
- Employed double-labeling experiments with 7-aminoactinomycin D (7AAD) and F4/80.
- Analyzed kidney tissue from embryonic days 11.5 to 16.5 in mice.
Main Results:
- Specialist macrophages, identified by F4/80, are present wherever cell death occurs in the developing kidney.
- Macrophages were observed to be engorged with phagocytosed apoptotic bodies, particularly from embryonic day 14.5.
- Double-labeling confirmed that the majority of dying cells are engulfed by macrophages.
Conclusions:
- Haemopoietically derived specialist macrophages are primarily responsible for clearing apoptotic cells during mouse kidney development.
- Efficient clearance of developmental cell death by macrophages is crucial for proper nephron formation and kidney morphogenesis.