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Macrophages kill capillary cells in G1 phase of the cell cycle during programmed vascular regression
G Diez-Roux1, M Argilla, H Makarenkova
1Developmental Genetics Program, Skirball Institute for Biomolecular Medicine, Department of Pediatrics, Division of Pediatric Cardiology, Kaplan Cancer Center, New York, NY, USA.
Abstract:
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 macrophage elimination, we show that during regression, macrophages induce apoptosis of both pericytes and endothelial cells in a cell cycle stage-dependent manner. Target cells are signaled to die by macrophages approximately 15 hours after S-phase labeling and this corresponds to a point in mid-G1 phase of the cell cycle. The tight correlation between the restriction point of the cell cycle and the point where the macrophage death signal is received suggests that the mitogen, matrix and cytoskeletal signals essential for cell-cycle progression may be inhibited by macrophages as a means of inducing 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 general phenomenon during development and homeostasis.
Insights
Macrophages trigger programmed cell death in pericytes and endothelial cells during eye development. This process, dependent on the cell cycle, reveals how macrophages can induce apoptosis in various cell types.
Area of Science:
- Developmental biology
- Cell biology
- Immunology
Background:
- Programmed capillary regression is a normal developmental process in the eye.
- This process is a valuable model for studying vascular involution.
- Macrophages play a role in developmental processes.
Purpose of the Study:
- To investigate the role of macrophages in programmed capillary regression.
- To determine the mechanism by which macrophages induce cell death in vascular cells.
- To understand the cell cycle dependency of macrophage-induced apoptosis.
Main Methods:
- Utilized S-phase labeling to track cell cycle progression.
- Employed liposome-mediated macrophage elimination to study macrophage function.
- Correlated cell death timing with specific cell cycle phases.
Main Results:
- Macrophages induce apoptosis in pericytes and endothelial cells during capillary regression.
- Cell death is triggered approximately 15 hours after S-phase labeling, corresponding to mid-G1 phase.
- Macrophage-induced cell death is dependent on the cell cycle stage of the target cells.
- Evidence suggests macrophages inhibit essential cell-cycle signals to induce apoptosis.
Conclusions:
- Macrophage-induced apoptosis is a general phenomenon during development and homeostasis.
- The cell cycle-dependent inhibition of signaling pathways by macrophages is a key mechanism for inducing cell death.
- This study provides insights into the role of macrophages in tissue remodeling and development.